Pub Date : 2024-05-18DOI: 10.1007/s11154-024-09886-w
Gie Ken-Dror, David Fluck, Michael E J Lean, Felipe F Casanueva, Thang Sieu Han
Prolactin (PRL) is secreted throughout life in men and women. At elevated levels, its physiological role in pregnancy and lactation, and pathological effects, are well known. However clinical implications of low circulating PRL are not well established. We conducted a meta-analysis to examine the relationship between low PRL levels and type 2 diabetes. Five papers included cross-sectional studies comprising 8,720 men (mean age range 51.4-60 years) and 3,429 women (49.5-61.6 years), and four papers included cohort studies comprising 2,948 men (52.1-60.0 years) and 3,203 women (49.2-60.1 years). Individuals with pregnancy, lactation and hyperprolactinemia, drugs known to alter circulating PRL levels, or pituitary diseases had been excluded. Although most studies used quartiles to categorize PRL groups for analysis, PRL cut-off values (all measured by chemiluminescence immunoassay) were variably defined between studies: the lowest PRL quartiles ranged from 3.6 ng/ml to 7.2 ng/ml in men and between 4.5 ng/ml to 8 ng/ml in women; and the highest PRL quartiles ranged from 6.9 ng/ml to 13 ng/ml in men and 9.6 ng/ml to 15.8 ng/ml in women. Type 2 diabetes was defined variably using self-reported physician's diagnosis, fasting blood glucose, oral glucose tolerance test or glycated hemoglobin (HbA1C). In cross-sectional studies, compared to individuals in the highest PRL groups (reference), those in the lowest PRL groups had greater risk of type 2 diabetes both in men: odds ratio (OR) and 95% confidence interval = 1.86 (1.56-2.22) and in women: OR = 2.15 (1.63-2.85). In cohort studies, women showed a significant association between low PRL and type 2 diabetes: OR = 1.52 (1.02-2.28) but not men: OR = 1.44 (0.46-4.57). Relatively low heterogeneity was observed (I2 = 25-38.4%) for cross-sectional studies, but higher for cohort studies (I2 = 52.8-79.7%). In conclusion, low PRL is associated with type 2 diabetes, but discrepancy between men and women in the relationship within cohort studies requires further research.
催乳素(PRL)在男性和女性的一生中都会分泌。在水平升高时,它在怀孕和哺乳期的生理作用以及病理影响已众所周知。然而,低水平的循环 PRL 对临床的影响尚未得到充分证实。我们进行了一项荟萃分析,研究低PRL水平与2型糖尿病之间的关系。五篇论文纳入了横断面研究,包括8720名男性(平均年龄范围为51.4-60岁)和3429名女性(49.5-61.6岁);四篇论文纳入了队列研究,包括2948名男性(52.1-60.0岁)和3203名女性(49.2-60.1岁)。这些研究排除了妊娠、哺乳和高催乳素血症患者、已知会改变循环 PRL 水平的药物或垂体疾病患者。虽然大多数研究使用四分位数来划分 PRL 组别进行分析,但不同研究对 PRL 临界值(均通过化学发光免疫测定法测量)的定义各不相同:最低 PRL 四分位数从 3.男性 PRL 最低四分位数介于 3.6 纳克/毫升至 7.2 纳克/毫升之间,女性介于 4.5 纳克/毫升至 8 纳克/毫升之间;男性 PRL 最高四分位数介于 6.9 纳克/毫升至 13 纳克/毫升之间,女性介于 9.6 纳克/毫升至 15.8 纳克/毫升之间。2 型糖尿病的定义各不相同,使用的是自我报告的医生诊断、空腹血糖、口服葡萄糖耐量试验或糖化血红蛋白 (HbA1C)。在横断面研究中,与 PRL 最高组(参照组)的人相比,PRL 最低组的人罹患 2 型糖尿病的风险更大,男性:几率比(OR)和 95% 置信区间 = 1.86(1.56-2.22),女性:几率比(OR)和 95% 置信区间 = 2.15(1.56-2.22):或=2.15(1.63-2.85)。在队列研究中,女性的低 PRL 与 2 型糖尿病之间存在显著关联:OR = 1.52 (1.02-2.28),而男性则不然:OR = 1.44 (0.46-4.57)。横断面研究的异质性相对较低(I2 = 25-38.4%),但队列研究的异质性较高(I2 = 52.8-79.7%)。总之,低PRL与2型糖尿病有关,但在队列研究中男女之间的关系存在差异,需要进一步研究。
{"title":"The relationship between low prolactin and type 2 diabetes.","authors":"Gie Ken-Dror, David Fluck, Michael E J Lean, Felipe F Casanueva, Thang Sieu Han","doi":"10.1007/s11154-024-09886-w","DOIUrl":"https://doi.org/10.1007/s11154-024-09886-w","url":null,"abstract":"<p><p>Prolactin (PRL) is secreted throughout life in men and women. At elevated levels, its physiological role in pregnancy and lactation, and pathological effects, are well known. However clinical implications of low circulating PRL are not well established. We conducted a meta-analysis to examine the relationship between low PRL levels and type 2 diabetes. Five papers included cross-sectional studies comprising 8,720 men (mean age range 51.4-60 years) and 3,429 women (49.5-61.6 years), and four papers included cohort studies comprising 2,948 men (52.1-60.0 years) and 3,203 women (49.2-60.1 years). Individuals with pregnancy, lactation and hyperprolactinemia, drugs known to alter circulating PRL levels, or pituitary diseases had been excluded. Although most studies used quartiles to categorize PRL groups for analysis, PRL cut-off values (all measured by chemiluminescence immunoassay) were variably defined between studies: the lowest PRL quartiles ranged from 3.6 ng/ml to 7.2 ng/ml in men and between 4.5 ng/ml to 8 ng/ml in women; and the highest PRL quartiles ranged from 6.9 ng/ml to 13 ng/ml in men and 9.6 ng/ml to 15.8 ng/ml in women. Type 2 diabetes was defined variably using self-reported physician's diagnosis, fasting blood glucose, oral glucose tolerance test or glycated hemoglobin (HbA<sub>1C</sub>). In cross-sectional studies, compared to individuals in the highest PRL groups (reference), those in the lowest PRL groups had greater risk of type 2 diabetes both in men: odds ratio (OR) and 95% confidence interval = 1.86 (1.56-2.22) and in women: OR = 2.15 (1.63-2.85). In cohort studies, women showed a significant association between low PRL and type 2 diabetes: OR = 1.52 (1.02-2.28) but not men: OR = 1.44 (0.46-4.57). Relatively low heterogeneity was observed (I<sup>2</sup> = 25-38.4%) for cross-sectional studies, but higher for cohort studies (I<sup>2</sup> = 52.8-79.7%). In conclusion, low PRL is associated with type 2 diabetes, but discrepancy between men and women in the relationship within cohort studies requires further research.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-11-22DOI: 10.1007/s11154-023-09853-x
Susana Rovira-Llopis, Clara Luna-Marco, Laura Perea-Galera, Celia Bañuls, Carlos Morillas, Victor M Victor
Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.
{"title":"Circadian alignment of food intake and glycaemic control by time-restricted eating: A systematic review and meta-analysis.","authors":"Susana Rovira-Llopis, Clara Luna-Marco, Laura Perea-Galera, Celia Bañuls, Carlos Morillas, Victor M Victor","doi":"10.1007/s11154-023-09853-x","DOIUrl":"10.1007/s11154-023-09853-x","url":null,"abstract":"<p><p>Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"325-337"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-01-11DOI: 10.1007/s11154-023-09865-7
Rosalind Walmsley, Lynn Chong, Michael W Hii, Robyn M Brown, Priya Sumithran
Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour.Registration code in PROSPERO: CRD42022313992.
{"title":"The effect of bariatric surgery on the expression of gastrointestinal taste receptors: A systematic review.","authors":"Rosalind Walmsley, Lynn Chong, Michael W Hii, Robyn M Brown, Priya Sumithran","doi":"10.1007/s11154-023-09865-7","DOIUrl":"10.1007/s11154-023-09865-7","url":null,"abstract":"<p><p>Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour.Registration code in PROSPERO: CRD42022313992.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"421-446"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.
骨关节炎(OA)是一种致残性疾病,也是最常见的身体退化性疾病之一,其病因多种多样,分子机制极为复杂,至今仍缺乏有效的治疗方法。设计生物网络和精确修改现有基因组位点的能力为医学和生物技术科学的应用带来了巨大潜力。CRISPR/Cas9 机制是其中一种高度特异性的基因组编辑技术,被称为簇状规则间隔短回文重复序列,它是一种由 CRISPR 相关蛋白 9(Cas9)构成的防御机制,由小的非编码 RNA(sncRNA)引导,通过沃森-克里克碱基配对规则与目标 DNA 结合,随后启动对目标 DNA 的修复。最新的研究证实,CRISPR/Cas9 机制能有效针对 OA 的遗传和表观遗传学改变,抑制或删除基因表达,并最终在体外和体内骨关节炎模型中发挥独特的抗关节炎特性。据报道,这种高通量和多路复用的基因编辑方法是一种简便、微创的技术,而且对骨关节炎患者来说痛苦相对较小,因此它可以极大地促进 OA 相关治疗方法的临床开发。
{"title":"Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.","authors":"Rexhina Vlashi, Xingen Zhang, Haibo Li, Guiqian Chen","doi":"10.1007/s11154-023-09860-y","DOIUrl":"10.1007/s11154-023-09860-y","url":null,"abstract":"<p><p>Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"339-367"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adipose tissue, including white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, is vital in modulating whole-body energy metabolism. While WAT primarily stores energy, BAT dissipates energy as heat for thermoregulation. Beige adipose tissue is a hybrid form of adipose tissue that shares characteristics with WAT and BAT. Dysregulation of adipose tissue metabolism is linked to various disorders, including obesity, type 2 diabetes, cardiovascular diseases, cancer, and infertility. Both brown and beige adipocytes secrete multiple molecules, such as batokines, packaged in extracellular vesicles or as soluble signaling molecules that play autocrine, paracrine, and endocrine roles. A greater understanding of the adipocyte secretome is essential for identifying novel molecular targets in treating metabolic disorders. Additionally, microRNAs show crucial roles in regulating adipose tissue differentiation and function, highlighting their potential as biomarkers for metabolic disorders. The browning of WAT has emerged as a promising therapeutic approach in treating obesity and associated metabolic disorders. Many browning agents have been identified, and nanotechnology-based drug delivery systems have been developed to enhance their efficacy. This review scrutinizes the characteristics of and differences between white, brown, and beige adipose tissues, the molecular mechanisms involved in the development of the adipocytes, the significant roles of batokines, and regulatory microRNAs active in different adipose tissues. Finally, the potential of WAT browning in treating obesity and atherosclerosis, the relationship of BAT with cancer and fertility disorders, and the crosstalk between adipose tissue with circadian system and circadian disorders are also investigated.
脂肪组织,包括白色脂肪组织(WAT)、棕色脂肪组织(BAT)和米色脂肪组织,对调节全身能量代谢至关重要。白色脂肪组织主要储存能量,而棕色脂肪组织则将能量转化为热量用于体温调节。米色脂肪组织是一种混合形式的脂肪组织,与 WAT 和 BAT 具有相同的特征。脂肪组织代谢失调与多种疾病有关,包括肥胖、2 型糖尿病、心血管疾病、癌症和不孕症。棕色和米色脂肪细胞都会分泌多种分子,如蝙蝠素,这些分子包装在细胞外囊泡中或作为可溶性信号分子,发挥自分泌、旁分泌和内分泌作用。进一步了解脂肪细胞分泌组对于确定治疗代谢紊乱的新分子靶点至关重要。此外,microRNAs 在调节脂肪组织分化和功能方面显示出至关重要的作用,突显了其作为代谢紊乱生物标志物的潜力。WAT褐变已成为治疗肥胖和相关代谢紊乱的一种很有前景的治疗方法。目前已确定了许多褐变剂,并开发了基于纳米技术的给药系统以提高其疗效。这篇综述仔细研究了白色、棕色和米色脂肪组织的特点和差异、脂肪细胞发育的分子机制、蝙蝠素的重要作用以及活跃于不同脂肪组织的调控微核糖核酸。最后,还研究了 WAT 褐化在治疗肥胖和动脉粥样硬化方面的潜力、BAT 与癌症和生育障碍的关系,以及脂肪组织与昼夜节律系统和昼夜节律紊乱之间的相互关系。
{"title":"An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications.","authors":"Zeinab Ghesmati, Mohsen Rashid, Shabnam Fayezi, Frank Gieseler, Effat Alizadeh, Masoud Darabi","doi":"10.1007/s11154-023-09850-0","DOIUrl":"10.1007/s11154-023-09850-0","url":null,"abstract":"<p><p>Adipose tissue, including white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, is vital in modulating whole-body energy metabolism. While WAT primarily stores energy, BAT dissipates energy as heat for thermoregulation. Beige adipose tissue is a hybrid form of adipose tissue that shares characteristics with WAT and BAT. Dysregulation of adipose tissue metabolism is linked to various disorders, including obesity, type 2 diabetes, cardiovascular diseases, cancer, and infertility. Both brown and beige adipocytes secrete multiple molecules, such as batokines, packaged in extracellular vesicles or as soluble signaling molecules that play autocrine, paracrine, and endocrine roles. A greater understanding of the adipocyte secretome is essential for identifying novel molecular targets in treating metabolic disorders. Additionally, microRNAs show crucial roles in regulating adipose tissue differentiation and function, highlighting their potential as biomarkers for metabolic disorders. The browning of WAT has emerged as a promising therapeutic approach in treating obesity and associated metabolic disorders. Many browning agents have been identified, and nanotechnology-based drug delivery systems have been developed to enhance their efficacy. This review scrutinizes the characteristics of and differences between white, brown, and beige adipose tissues, the molecular mechanisms involved in the development of the adipocytes, the significant roles of batokines, and regulatory microRNAs active in different adipose tissues. Finally, the potential of WAT browning in treating obesity and atherosclerosis, the relationship of BAT with cancer and fertility disorders, and the crosstalk between adipose tissue with circadian system and circadian disorders are also investigated.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"279-308"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-07-28DOI: 10.1007/s11154-023-09826-0
Noemi Salmeri, Paola Viganò, Paolo Cavoretto, Roberto Marci, Massimo Candiani
Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with a significant impact on the health and quality of life of women affected. A novel hypothesis by evolutionary biologists suggested that these two diseases are inversely related to one another, representing a pair of diametrical diseases in terms of opposite alterations in reproductive physiological processes but also contrasting phenotypic traits. However, to fully explain the phenotypic features observed in women with these conditions, we need to establish a potential nexus system between the reproductive system and general biological functions. The recent discovery of kisspeptin as pivotal mediator of internal and external inputs on the hypothalamic-pituitary-gonadal axis has led to a new understanding of the neuroendocrine upstream regulation of the human reproductive system. In this review, we summarize the current knowledge on the physiological roles of kisspeptin in human reproduction, as well as its involvement in complex biological functions such as metabolism, inflammation and pain sensitivity. Importantly, these functions are known to be dysregulated in both PCOS and endometriosis. Within the evolving scientific field of "kisspeptinology", we critically discuss the clinical relevance of these discoveries and their potential translational applications in endometriosis and PCOS. By exploring the possibilities of manipulating this complex signaling system, we aim to pave the way for novel targeted therapies in these reproductive diseases.
{"title":"The kisspeptin system in and beyond reproduction: exploring intricate pathways and potential links between endometriosis and polycystic ovary syndrome.","authors":"Noemi Salmeri, Paola Viganò, Paolo Cavoretto, Roberto Marci, Massimo Candiani","doi":"10.1007/s11154-023-09826-0","DOIUrl":"10.1007/s11154-023-09826-0","url":null,"abstract":"<p><p>Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with a significant impact on the health and quality of life of women affected. A novel hypothesis by evolutionary biologists suggested that these two diseases are inversely related to one another, representing a pair of diametrical diseases in terms of opposite alterations in reproductive physiological processes but also contrasting phenotypic traits. However, to fully explain the phenotypic features observed in women with these conditions, we need to establish a potential nexus system between the reproductive system and general biological functions. The recent discovery of kisspeptin as pivotal mediator of internal and external inputs on the hypothalamic-pituitary-gonadal axis has led to a new understanding of the neuroendocrine upstream regulation of the human reproductive system. In this review, we summarize the current knowledge on the physiological roles of kisspeptin in human reproduction, as well as its involvement in complex biological functions such as metabolism, inflammation and pain sensitivity. Importantly, these functions are known to be dysregulated in both PCOS and endometriosis. Within the evolving scientific field of \"kisspeptinology\", we critically discuss the clinical relevance of these discoveries and their potential translational applications in endometriosis and PCOS. By exploring the possibilities of manipulating this complex signaling system, we aim to pave the way for novel targeted therapies in these reproductive diseases.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"239-257"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9886708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-12-02DOI: 10.1007/s11154-023-09854-w
Lucas Paulo Jacinto Saavedra, Silvano Piovan, Veridiana Mota Moreira, Gessica Dutra Gonçalves, Anna Rebeka Oliveira Ferreira, Maiara Vanusa Guedes Ribeiro, Maria Natália Chimirri Peres, Douglas Lopes Almeida, Scarlett Rodrigues Raposo, Mariane Carneiro da Silva, Letícia Ferreira Barbosa, Paulo Cezar de Freitas Mathias
Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility.
{"title":"Epigenetic programming for obesity and noncommunicable disease: From womb to tomb.","authors":"Lucas Paulo Jacinto Saavedra, Silvano Piovan, Veridiana Mota Moreira, Gessica Dutra Gonçalves, Anna Rebeka Oliveira Ferreira, Maiara Vanusa Guedes Ribeiro, Maria Natália Chimirri Peres, Douglas Lopes Almeida, Scarlett Rodrigues Raposo, Mariane Carneiro da Silva, Letícia Ferreira Barbosa, Paulo Cezar de Freitas Mathias","doi":"10.1007/s11154-023-09854-w","DOIUrl":"10.1007/s11154-023-09854-w","url":null,"abstract":"<p><p>Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"309-324"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-12-05DOI: 10.1007/s11154-023-09858-6
Rosaria M Ruggeri, Irene Aini, Stefano Gay, Erika Maria Grossrubatscher, Camilla Mancini, Maria Grazia Tarsitano, Virginia Zamponi, Andrea M Isidori, Annamaria Colao, Antongiulio Faggiano
As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.
{"title":"Efficacy and tolerability of somatostatin analogues according to gender in patients with neuroendocrine tumors.","authors":"Rosaria M Ruggeri, Irene Aini, Stefano Gay, Erika Maria Grossrubatscher, Camilla Mancini, Maria Grazia Tarsitano, Virginia Zamponi, Andrea M Isidori, Annamaria Colao, Antongiulio Faggiano","doi":"10.1007/s11154-023-09858-6","DOIUrl":"10.1007/s11154-023-09858-6","url":null,"abstract":"<p><p>As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"383-398"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-12-04DOI: 10.1007/s11154-023-09856-8
Thiago Dos Reis Araujo, Bruna Lourençoni Alves, Lohanna Monali Barreto Dos Santos, Luciana Mateus Gonçalves, Everardo Magalhães Carneiro
Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life. This hypothesis was postulated and confirmed until today by several studies that demonstrate that experimental models submitted to protein undernutrition present alterations in glycemic homeostasis linked, in part, to the reduction of insulin secretion. Therefore, understanding the changes that lead to a reduction in the secretion of this hormone is essential to prevent the development of diabetes in undernourished individuals. This narrative review aims to describe the main molecular changes already characterized in pancreatic β cells that will contribute to the reduction of insulin secretion in protein undernutrition. So, it will provide new perspectives and targets for postulation and action of therapeutic strategies to improve glycemic homeostasis during this nutritional deficiency.
{"title":"Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.","authors":"Thiago Dos Reis Araujo, Bruna Lourençoni Alves, Lohanna Monali Barreto Dos Santos, Luciana Mateus Gonçalves, Everardo Magalhães Carneiro","doi":"10.1007/s11154-023-09856-8","DOIUrl":"10.1007/s11154-023-09856-8","url":null,"abstract":"<p><p>Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life. This hypothesis was postulated and confirmed until today by several studies that demonstrate that experimental models submitted to protein undernutrition present alterations in glycemic homeostasis linked, in part, to the reduction of insulin secretion. Therefore, understanding the changes that lead to a reduction in the secretion of this hormone is essential to prevent the development of diabetes in undernourished individuals. This narrative review aims to describe the main molecular changes already characterized in pancreatic β cells that will contribute to the reduction of insulin secretion in protein undernutrition. So, it will provide new perspectives and targets for postulation and action of therapeutic strategies to improve glycemic homeostasis during this nutritional deficiency.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":"259-278"},"PeriodicalIF":6.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}