Reviews in Endocrine & Metabolic Disorders最新文献

Obesity is a global public health challenge intimately linked to cardiometabolic complications. Although current anti-obesity medications can produce substantial and rapid weight loss, their discontinuation often results in rapid weight regain, underscoring the urgent need for therapies that support long-term weight loss maintenance. The ghrelin receptor system, comprising the hormone ghrelin and its receptor growth hormone secretagogue receptor 1a (GHSR1a), has long been a target for appetite regulation, but decades of drug development have yielded limited clinical success. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous GHSR1a antagonist and inverse agonist, has reignited interest in this pathway. LEAP2 suppresses appetite in both rodents and humans, and optimized analogs have shown modest but promising metabolic effects in preclinical models. Although less potent than currently leading agents, LEAP2-based therapies may offer value as adjunct treatments, particularly for sustaining weight loss. This review explores the evolving therapeutic potential of the GHSR1a pathway, with a particular focus on LEAP2 as a novel strategy for treating obesity and associated cardiometabolic disorders.

People with type 2 diabetes have higher rates of hypertension compared to the general population, Current guidelines do not consider the baseline blood pressure for activity prescription. This study aimed to evaluate and compare effects of different physical activity modalities on blood pressure in individuals with type 2 diabetes mellitus considering baseline blood pressure levels and exploring the dose-response relationship. A systematic search was performed in CINAHL, EMBASE, MEDLINE, Scopus, SportDiscus and WOS databases to June 2025. A dose-response network meta-analysis of 71 trials (3,970 participants) was conducted. Studies included individuals with type 2 diabetes who underwent any physical activity intervention with reported blood pressure outcomes. Meta-regressions included baseline blood pressure as a covariate. Aerobic activity significantly reduced systolic blood pressure (SBP) in stage 1 (-5.37 mmHg) and stage 2 hypertension (-8.32 mmHg). Mind-body activities showed notable effects, particularly in more severe hypertension (-13.35 mmHg). Resistance training was most effective for elevated SBP. Both aerobic and mind-body exercises improved diastolic blood pressure (DBP). A significant overall dose-response association was found, but it was not maintained when analyses were stratified by exercise modality, indicating that the observed benefits likely reflect overall physical activity exposure rather than modality-specific effects. Resistance training may be most effective for elevated SBP, aerobic activity for stage 1-2 systolic hypertension, and mind-body therapies for more severe diastolic hypertension. Optimal effects were achieved at approximately 826 and 994 METs-min/week for SBP and DBP, respectively.

Estrogens are a group of steroid hormones that exert a key role in female sexual and reproductive development and function. Produced primarily in the ovaries, estrogens influence many different aspects of physiology such as temperature homeostasis, feeding behavior, locomotor activity and glucose homeostasis by acting at the central nervous system. In particular, these endocrine factors interact with different hypothalamic nuclei in order to exert an increase in body temperature, anorectic effect, increased locomotion and improved glucose handling. Estrogenic actions can be mediated through several receptors, including the estrogen receptor-α (ERα), estrogen receptor-β (ERβ) and G protein-coupled estrogen receptor 1 (GPER1). Among these, ERα is well established to be one key receptor mediating estrogenic actions on energy balance partially through its transcriptional activity as a nuclear receptor. In addition to the transcriptional activities, E2 can also trigger rapid signaling cascades in the hypothalamus where AMPK, cAMP, PI3K, mTOR and ceramides, have all been implicated to mediate metabolic actions of E2. Moreover, E2 can induce in neurons super-fast excitations through the membrane-bound ERα. A putative membrane ER coupled to Gq (Gq-mER) has been proposed to mediate E2 actions on G protein-gated inwardly rectifying potassium GIRK, on the small conductance calcium-activated potassium (SK) currents, and on the ATP-sensitive potassium (K_ATP) currents in hypothalamic neurons. Finally, a chloride ion channel (Clic1) was recently proposed to mediate E2-induced excitation of ERα-expressing neurons in the hypothalamus. This article will review recent advances in understanding these neurobiological processes regulated by estrogens and the associated molecular mechanism.

The hypothalamus is arguably the most complex part of the brain, with the greatest heterogeneity of cellular populations. It is an integration center for peripheral signals and external stimuli and plays a key role in coordinating a myriad of fundamental biological functions, including energy homeostasis. To fully understand how the hypothalamus functions, we first need to unravel cellular heterogeneity of this brain region. In hypothalamic research, the vast majority of 'ground truths' have, until recently, emerged from low-throughput murine studies. However, the advent of high-throughput, single-cell approaches has dramatically altered the landscape and allow characterization of gene and protein expression, epigenomic features, cell morphology, and spatial organization. Recently, three-dimensional transcriptomic atlases of the macaque and human hypothalamus have been published and serve as growing resources for understanding hypothalamic cell types and organization in both healthy and disease states. Hypothalamic function is still primarily studied with the use of model systems, where cell culture methods are especially suitable for investigating molecular mechanisms, while animal models provide the opportunity to disentangle complex neural circuits as well as measure behavior and physiological changes. Here, we review what the latest technological advancements and functional discoveries have revealed to us about the hypothalamus, with a focus on feeding behavior.

The "Warburg effect", a metabolic adaptation observed in dividing cells, involves a shift from mitochondrial oxidative phosphorylation to cytoplasmic glucose metabolism. This metabolic process is characterized by increased cellular uptake of glucose and glutamine, elevated intracellular pH and sodium levels, enhanced protection against oxidative stress, altered autophagy, and increased lactate production. Initially identified by Otto Warburg in cancer cells, the Warburg effect is now recognized as a common feature of all dividing cells, prioritizing biomass production for cell proliferation over energy generation for specialized cellular functions. Indeed, the Warburg effect is emerging as an important feature not only in cancer but also in a range of metabolic, endocrine, and neurological chronic disorders, including type 2 diabetes, heart and kidney failure, therapy-refractory epilepsy, Alzheimer's and Parkinson's diseases, chronic fatigue syndrome, and post-viral syndromes. The prevailing notion that "dysfunctional mitochondria" are the primary cause of the "energy deficit" observed in these conditions may be misleading. Instead, this "energy deficit" can result from cells reprogramming their metabolism to support cell division. Additionally, in these disorders, senescent cells are abundant, exhibiting a Warburg-like metabolism with cell cycle arrest and enhanced anabolic activity. This review explores the multifaceted role of the Warburg effect in type 2 diabetes and other metabolic and endocrine chronic disorders and examines the therapeutic potential of different interventions such as intermittent fasting, ketogenic diets, ketone supplements, and sodium/glucose co-transporter 2 inhibitors. Through a comprehensive analysis of existing literature, we aim to shed light on the mechanisms underlying these interventions and their potential impact on disease progression and patient outcomes.

Childhood obesity is a significant concern and its chronic nature results in an increased risk of adulthood obesity. Poorly planned transition from pediatric to adult care may contribute to poor outcomes. Failed transition may result in loss to follow-up or inadequate treatment adherence. In other chronic diseases, the transition is well organized. However, although obesity societies highlight its importance, no specific guidelines are available to properly accomplish this procedure. In order to fill this gap, an interdisciplinary group consisting of pediatric endocrinologists, adult endocrinologists and primary care practitioners combined forces to develop a set of agreed recommendations to guide the transition of adolescents living with obesity (AlwOs) from pediatric to adult healthcare. Three well-defined phases were identified: preparation of transfer, transfer and reception in adult care. Specific suggestions, accompanied by infographic support, are provided for each one of them. The authors agreed to underline several important issues: there is no ideal age to initiate transition, which is contingent upon individual characteristics; the figure of a transition coordinator is pivotal; pre-transfer sessions with participation of pediatric and adult teams are required to guarantee continuity of care; transfer should start only if AlwO/caregivers agree; transfer sessions should start under control of the pediatric provider, and leadership should be progressively taken over by the adult doctor, who should be adequately trained to manage patients with a troublesome condition at a critical age; at reception in adult care, a detailed long-term management and follow-up plan has to be agreed with the AlwO. Finally, tools to assess quality of the procedure are provided. In summary, guidance to manage the AlwO's transition in the daily practice is supplied.

Impulsivity is a personality trait composed of (food) reward sensitivity and inhibitory control. We have systematically synthesized evidence from prospective studies on broadly conceptualized impulsivity as agent and/or object of change within obesity surgery interventions. Using the PRISMA statement, studies were identified from a PubMed and PsychInfo search. We included studies investigating individuals with obesity undergoing surgery for weight loss which reported for the influence of impulsivity on surgery outcome and/or the effect of surgery on impulsivity as assessed by self-report or laboratory tasks. Our search resulted in 783 articles of which 40 articles were selected. Most evidence stems from self-report on food-related impulsivity using the Three-Factor Eating Questionnaire (TFEQ). We found consistent evidence that self-reported food-related impulsivity is not a predictor of weight outcome after obesity surgery and that impulsivity is decreased after surgey. There is preliminary evidence that baseline brain activity patterns in reward- and inhibition-related regions might predict surgery-induced weight loss. Post-surgery impulsivity levels and pre-post-changes in impulsivity were found to be predictive of surgery-induced weight loss. Evidence suggests a potential pathway of dynamic post-surgery self-amplifying interactions between surgery-induced physiological changes, impulsivity and its behavioral components and long-term weight development. Interventions fostering post-surgery decrease in impulsivity could improve treatment success and prevent weight regain.

The hypothalamus is a singular brain region with essential roles in the control of a wide diversity of vegetative functions, from growth and energy balance to reproduction. These processes are governed by interconnected neuroendocrine pathways that enable proper adjustment of fundamental biological programs to internal and external cues along the lifespan. Puberty is a key maturational phenomenon that permits full sexual and somatic maturation, and attainment of reproductive capacity, together with important psychological changes. Puberty is to a large extent, a brain-driven phenomenon, with the hypothalamus playing a major role as the essential hub for the integration of central and peripheral signals, responsible for driving puberty onset and its modulation by endogenous and environmental factors. Our understanding of the hypothalamic circuits governing puberty has expanded enormously in the last decades, as exemplified by the discovery and later characterization of the roles of neurons producing kisspeptins, aka Kiss1 neurons, as major gatekeepers of puberty onset, mainly through their role as indispensable upstream activators of GnRH neurons. In recent years, the intimate molecular programs and co-players of Kiss1 neurons that participate in pubertal control have been partially exposed. In addition, given the paramount importance of metabolic signals in the modulation of puberty, the nature and mechanisms of action of different factors, converging at the hypothalamus, that participate in pubertal modulation by the metabolic and nutritional status have been disclosed. While characterization of these regulatory circuits is still uncomplete, this review aims to provide a synoptic and updated view of our current knowledge of the essential elements responsible for the hypothalamic control of puberty, also as a means to understand the putative basis for acquired pubertal disorders, including those linked to metabolic perturbations, such as early-onset obesity or undernutrition.

Diabetic foot ulcers (DFUs) are among the most serious complications of diabetes mellitus, often resulting in infection, amputation, and increased mortality. Early detection is essential but remains difficult due to the complex interaction of neuropathy, vascular disease, and immune dysfunction. This review examines the effectiveness of thermal imaging, including approaches supported by artificial intelligence (AI), as a non-invasive tool for identifying early signs of DFUs. A total of 49 studies published between 1991 and 2024 were analysed, focusing on adult patients and primary research only. Findings show that thermal imaging can detect abnormal skin temperature patterns and early inflammation, key indicators of DFU development. AI techniques, such as machine learning and neural networks, further enhance diagnostic accuracy by identifying subtle patterns and predicting ulcer risk. Despite promising results, several limitations were noted: lack of standardised imaging protocols, inconsistent equipment quality, and small sample sizes in many studies. To improve clinical reliability, future work should focus on developing standard procedures, integrating AI with high-resolution thermal cameras, and validating these systems in real-world hospital and home-care settings. Overall, thermal imaging, especially when combined with AI, shows strong potential as a practical, non-invasive method for early DFU detection and monitoring.