Apolipoprotein CIII correlates with lipoproteins in the fed state and is not regulated by leptin administration in states of hypoleptinemia induced by acute or chronic energy deficiency: Results from two randomised controlled trials

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Background Medications targeting the leptin and Apolipoprotein CIII (APOC3) pathways are currently under development for treatment of hypertriglyceridaemia. Given that both implicated in triglyceride regulation, it is unknown whether they function independently or interact physiological conditions acute long‐term energy deficiency. Methods APOC3 levels their association with circulating lipids lipoproteins were evaluated context two randomised controlled studies. In Study‐1, 15 healthy individuals examined three distinct conditions, each lasting 72 h: isocaloric feeding, fasting placebo administration administered at replacement doses. Study‐2, 20 females hypoleptinemia due to relative deficiency sport (REDs) a minimum 6 months treated either 36 weeks. Results remained stable across all arms unaffected by administration. fed state, presented positive correlations various VLDL, IDL, LDL HDL sizes, free fatty acids (FFA), most which not replicated fasting. During complete deprivation, was correlated molecules, glutamine FFA, whereas its positively associated only FFA treatment. lower group, but this leptin‐dependent effect. A correlation between observed group. Conclusions These results contribute towards our better understanding intricate nature lipid regulation deficiency, suggesting medications act through different metabolic thus may have independent effects from other regulating triglycerides.

Language: Английский

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Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2320 - 2320

Published: March 5, 2025

Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) glucose-dependent insulinotropic polypeptide (GIP), impairing effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) interleukin-6 (IL-6), impair receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. dysfunction GDM associated with duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), mitochondrial leading impaired ATP production glucose-stimulated secretion. Excessive gestational weight gain exacerbates resistance through hyperleptinemia, which downregulates expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation skeletal muscle, GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids activate C, inhibiting 11β-hydroxysteroid dehydrogenase type (11β-HSD1) overactivity elevates cortisol levels, glucocorticoid receptors further reduce sensitivity. diagnostic thresholds (≥92 mg/dL fasting, ≥153 post-load) are lower than 2 prevent fetal hyperinsulinemia macrosomia. Management strategies focus on lifestyle modifications, dietary carbohydrate restriction exercise. Pharmacological interventions, or metformin, aim restore AMPK signaling hepatic output. Emerging therapies, (GLP-1R) agonists, show potential improving glycemic control reducing inflammation. A mechanistic understanding of essential for developing targeted therapeutic both adverse pregnancy outcomes the progression overt affected women.

Language: Английский

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The mediating role of BMI in the relationship between OSAHS and bone metabolism in male patients with T2DM

Sleep And Breathing, Journal Year: 2025, Volume and Issue: 29(2)

Published: April 12, 2025

Language: Английский

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Gallstones in the Era of Metabolic Syndrome: Pathophysiology, Risk Prediction, and Management

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Gallstone disease (GSD) and metabolic syndrome (MetS) are increasingly prevalent conditions with significant global health implications. Recent evidence highlights a strong epidemiological association between these disorders, driven by shared pathophysiological mechanisms. This review provides comprehensive analysis of the intricate relationship MetS GSD, focusing on role insulin resistance, dyslipidemia, obesity, gut microbiota dysbiosis in gallstone formation. An integrated model is proposed, linking disturbances to bile cholesterol supersaturation, gallbladder dysmotility, chronic inflammation. The also explores clinical implications, including risk prediction models based parameters, early detection biomarkers, targeted interventions such as lifestyle modifications, pharmacological therapies, microbiome modulation. By addressing underpinnings this synthesis offers foundation for developing preventive therapeutic strategies mitigate burden interconnected conditions. Future research directions outlined refine mechanistic insights improve outcomes.

Language: Английский

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Brown adipose tissue transplantation ameliorates hindlimb ischemic damage in diabetic mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 14, 2025

Peripheral arterial disease (PAD) is a common complication associated with diabetes, which can lead to foot ischemia. The condition often accompanied by infection and necrosis, ultimately leading diabetic ulcers the risk of amputation. Brown adipose tissue (BAT) its secreted cytokines play an essential role in regulation glucose homeostasis, modulation inflammatory responses, vascular endothelial cell proliferation. transplantation BAT into ischemic regions may offer therapeutic benefits alleviating symptoms PAD. A mouse model was established via intraperitoneal administration streptozocin. Subsequently, lower limb ulcer constructed transection femoral artery ligation vein. harvested from subscapular region employed as graft. research utilized Laser Doppler monitoring, Western blot analysis, hematoxylin-eosin (HE) staining, immunofluorescence enzyme-linked immunosorbent assay (ELISA) evaluate blood flow recovery regions, histopathological changes, angiogenesis remodeling, M1/M2 macrophage polarization. significantly enhanced mice while concurrently reducing necrotic tissue. Pathological analyses demonstrate that mitigates damage, stimulates angiogenesis, supports remodeling. Furthermore, blotting, immunofluorescence, ELISA results revealed reduces levels tissues, increases expression angiogenic factors, promotes polarization macrophages M1 M2 phenotype. has demonstrated mitigate injury mice, attenuate facilitate restoration flow. These effects be linked alterations

Language: Английский

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