The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation

Metabolism, Journal Year: 2024, Volume and Issue: unknown, P. 156057 - 156057

Published: Oct. 1, 2024

Language: Английский

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Leptin physiology and pathophysiology in energy homeostasis, immune function, neuroendocrine regulation and bone health

Metabolism, Journal Year: 2024, Volume and Issue: 161, P. 156056 - 156056

Published: Oct. 30, 2024

Language: Английский

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Leptin in humans: Evidence from clinical studies and current and future clinical applications

Metabolism, Journal Year: 2024, Volume and Issue: 161, P. 156053 - 156053

Published: Oct. 28, 2024

Leptin has been established as the prototype adipose tissue secreted hormone and a major regulator of several human physiology functions. Here, we are primarily reviewing findings from studies in humans involving leptin administration. We describing metabolic, endocrine immunologic effects replacement conditions deficiency, such short-term fasting healthy individuals, relative energy deficiency sports (REDS), congenital (CLD), generalized (GL) partial lipodystrophy (PL), HIV-associated (HIV-L) treatment excess (common obesity, type 2 diabetes, steatotic liver disease). comparing results with preclinical models present main conclusions regarding role physiology, pathophysiology therapeutics. conclude that, substitution effectively reduces body weight fat mass through reduction appetite, it improves hypertriglyceridemia, insulin resistance hepatic steatosis (especially GL PL), restores neuroendocrine function gonadotropic axis), regulates adaptive immune system cell populations bone health. On contrary, excess, common obesity does not improve any metabolic abnormalities. Strategies to overcome tolerance/resistance diabetes have provided promising animal studies, which should though be tested randomized clinical trials.

Language: Английский

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Accurate non-invasive detection of MASH with fibrosis F2-F3 using a lightweight machine learning model with minimal clinical and metabolomic variables

Metabolism, Journal Year: 2024, Volume and Issue: 163, P. 156082 - 156082

Published: Nov. 19, 2024

Language: Английский

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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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Adverse drug events associated with metreleptin administration: a real-world pharmacovigilance study from 2014 to 2024 using the FAERS database

Expert Opinion on Drug Safety, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

This study analyzed adverse drug event (ADE) signals associated with metreleptin using the FDA Adverse Event Reporting System (FAERS) to provide insights for safe clinical use.

Language: Английский

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