Archives of Physiology and Biochemistry最新文献

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2^+/+ and AMPKα2^-/- mice. Myotubes from AMPKα2^-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2^+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2^-/- mice. Proteomics analysis revealed that AMPKα2^-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.

Background: Lipid metabolism, one of the three major metabolic processes, plays a crucial role in male fertility, particularly when lipid homeostasis is disrupted. Lipid droplets (LDs), cellular organelles that store lipids primarily in the form of triglycerides and cholesterol esters, serve as central hubs in lipid metabolism.The degradation of LDs is regulated by lipases and lipophagy.

Objective:: This review explores the various forms of lipophagy, its molecular mechanisms, and its critical role in male fertility. Specifically, it examines the association between lipophagy and male infertility, sexual dysfunction, and reproductive cancers.

Methods:: This review synthesizes current research on the molecular pathways regulating lipophagy, focusing on its impact on male reproductive health.

Results:: Lipophagy is essential for maintaining lipid homeostasis in male reproductive tissues. Dysfunction of lipophagy is associated with impaired sperm function, infertility, sexual dysfunction, and an increased risk of reproductive cancers in men.

Conclusion:: Lipophagy plays a pivotal role in regulating lipid metabolism and maintaining male fertility. It may serve as a potential therapeutic target for treating male reproductive disorders.

Objective: This research assesses renoprotective effects of saracatinib (Src) in diabetic nephropathy (DN) and the potential underlying processes.

Materials and methods: Rats were divided into: control, DN, DN + Met + Los, DN + Met + Src, and DN + Met + Los + Src. Rats' ABP, urinary albumin, urinary nephrin, and creatinine clearance were assessed. Blood samples were collected for measuring glycaemic state parameters, renal functions, oxidative stress markers, inflammatory mediators, aldosterone, and lipid profile. Kidneys were extracted for KIM-1 and nephrin gene expression, H&E, Masson's trichrome staining, and immunohistochemical assessment.

Results: Significant increases in ABP, urinary albumin and nephrin, glycaemic measurements, urea, creatinine, aldosterone, inflammatory cytokines, MDA, lipids, renal fibrosis, H scores of VEGF and TGF-β, and renal KIM-1 expression were related to DN. However, there was a significant decrease in creatinine clearance, GSH, and nephrin expression in DN group compared with control group.

Discussion and conclusion: The combination of metformin (Met), losartan (Los), and Src repaired DN alterations. Adding Src to Met and Los is superior to using them alone.

This study explored the effects of melatonin on cardiac and vascular function, and redox homeostasis in model PAH. Male Wistar rats were divided into: control (CTR), monocrotaline [MCT (60 mg/kg, single dose i.p)], monocrotaline + sildenafil [MCT + SIL (50 mg/kg/day)], and monocrotaline + melatonin [MCT + MEL (10 mg/kg/day)]. This protocol lasted 21 days. Echocardiographic, morphometric, histological, vascular reactivity, and oxidative/nitrosative stress analyses were performed. The reduced diastolic function and AT/ET ratio in the MCT group were partially attenuated by melatonin and sildenafil treatment (p < 0.05). Increased RV hypertrophy and pulmonary congestion were reduced by both treatments (p < 0.05). MCT-induced pulmonary arteriolar muscle layer hypertrophy was also reduced by both treatments (p < 0.05). MCT and MCT + SIL present diminished vasorelaxation as compared to control (p < 0.05). Augmented oxidative/nitrosative stress and reduced glutathione-s-transferase activity in MCT were mitigated by both treatments (p < 0.05). Then, melatonin was as effective as sildenafil against PAH-induced oxidative stress and pathological vascular remodelling.

Sustained adrenergic overload in the heart causes maladaptive cardiac remodelling, which involves oxidative stress. Boldine (BOL) has antioxidant activity and represents a novel therapeutic approach. This study explored the cardioprotective role of BOL in adverse left ventricular remodelling induced by isoproterenol. The rats were divided into four groups: control; BOL (25 mg/kg daily); isoproterenol (ISO) (5 mg/kg daily), and ISO + BOL. Morphometric, echocardiographic, and oxidative stress parameters were evaluated. BOL attenuated both cardiac hypertrophy and increased diastolic volume caused by adrenergic overstimulation (P < 0.05). BOL treatment reduced lipid peroxidation induced by ISO (ISO vs. ISO + BOL; P < 0.05), and this effect was associated with increased superoxide dismutase (SOD) (ISO vs. ISO + BOL; P < 0.05) and glutathione-S-transferase levels (GST) (ISO vs. ISO + BOL; P < 0.05). This data suggest that BOL may improve cardiac oxidative stress and attenuate some parameters of adverse cardiac remodelling.

Introduction: Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota.

Method: A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota.

Result: A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases.

Conclusion: Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.

Introduction: Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.

Mechanism: During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.

Result and conclusion: These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.

Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto (Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells.

Introduction: A growing number of studies have thus far showed the association between type 2 diabetes mellitus (DM) and the intestinal microbiome homoeostasis. As reported, the gut microflora can be significantly different in patients with type 2 DM (T2DM) compared to those in healthy individuals.

Methods: The authors collected the relevant articles published until 2022 and these are carefully selected from three scientific databases based on keywords.

Discussion: This review highlights research on the anti-diabetic properties of berberine (BBR)-induced glucagon-like peptide-1 (GLP-1), as a glucose-lowering factor and a balance regulator in the microbial flora of the intestines, which plays an important role in adjusting the signalling pathways affecting insulin secretion.

Results: Considering the anti-diabetic characteristics of the BBR-induced GLP-1, BBR makes a promising complementary treatment for reducing the clinical symptoms of DM by reducing the hyperglycaemia. Berberin might be a safe and effective drug for T2DM with little or no adverse effects.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. The mechanism by which bisphenol A (BPA) promots NAFLD remains unclear. Palmitic acid (PA) and lipopolysaccharide (LPS) were used to simulate NAFLD in HepG2 cells in vitro. Total cholesterol (TC), triglyceride (TG) content, and lipid accumulation were measured to evaluate lipid metabolism. The caspase-1-stained cells and NLRP3 inflammasome-associated proteins were evaluated for pyroptosis. Western blot analysis was used to detect protein levels and co-immunoprecipitation (Co-IP) was used to detect the association between the proteins. Cycloheximide (CHX) treatment combined with western blot was performed to access protein stability. This data have shown that BPA induces lipid metabolism dysfunction and pyroptosis by upregulating O-GlcNAc transferase (OGT) level. NLRP3 directly interacts with OGT, and elevated OGT enhanced the stability of NLRP3 protein. BPA promoted OGT-mediated O-GlcNAcylation to stabilised NLRP3, thus accelerating NAFLD progress in vitro. Our study reveals that BPA, as an environmental factor, may be involved in the promotion of NAFLD, and that targeting NLRP3 and OGT may inhibit BPA's induction of NAFLD.