Leptin in humans: Evidence from clinical studies and current and future clinical applications DOI Creative Commons
Nikolaos Perakakis, Christos S. Mantzoros

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

Obesity and diabetes DOI
Chrysoula Boutari,

Antea DeMarsilis,

Christos S. Mantzoros

et al.

Diabetes Research and Clinical Practice, Journal Year: 2023, Volume and Issue: 202, P. 110773 - 110773

Published: June 24, 2023

Language: Английский

Citations

59
Relative Energy Deficiency in Sport (REDs): Endocrine Manifestations, Pathophysiology and Treatments DOI Creative Commons
Angeliki M. Angelidi, Konstantinos Stefanakis, Sharon H. Chou

et al.

Endocrine Reviews, Journal Year: 2024, Volume and Issue: 45(5), P. 676 - 708

Published: March 14, 2024

Research on lean, energy-deficient athletic and military cohorts has broadened the concept of Female Athlete Triad into Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum abnormalities induced by low energy availability (LEA), which serves as underlying cause all symptoms described within concept, affecting exercising populations either biological sex. Both short- long-term LEA, conjunction with other moderating factors, may produce multitude maladaptive changes that impair various physiological systems adversely affect health, well-being, sport performance. Consequently, comprehensive definition encompasses broad sequelae adverse clinical outcomes related to such neuroendocrine, bone, immune, hematological effects, ultimately resulting compromised health In this review, we discuss pathophysiology associated disorders. We briefly examine current treatment recommendations for REDs, primarily focusing nonpharmacological, behavioral, lifestyle modifications target its cause-energy deficit. also approaches aimed at managing symptoms, menstrual dysfunction bone stress injuries, explore potential novel treatments physiology, emphasizing roles leptin activin-follistatin-inhibin axis, remain be fully elucidated, management REDs. near future, therapies leveraging our emerging understanding molecules axes or lack thereof restore LEA-related abnormalities, thus preventing and/or treating REDs-related complications, fractures, improving

Language: Английский

Citations

18
Energy metabolism in health and diseases DOI Creative Commons
Hui Liu, Shuo Wang, Jianhua Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

Citations

9
Obesity and Chronic Inflammation: Implications for Rheumatoid Arthritis, Spondyloarthritis, and Ulcerative Colitis DOI Creative Commons

Ada Corrado,

I. Guadagni,

Giovanna Picarelli

et al.

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

Immune-mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and persistent inflammation. Rheumatoid arthritis (RA), spondyloarthritis (SpA), ulcerative colitis (UC) exemplify prominent IMIDs, each presenting unique challenges for their management, that impact patient's quality life (QoL). Obesity, marked low-grade inflammation, influences the progression, response to treatment, clinical management patients with RA, SpA, UC. Besides, emerging role sarcopenic obesity, special subtype obesity malnutrition, should be considered in definition appropriated therapeutic interventions.

Language: Английский

Citations

2
Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy DOI Open Access
Angeliki M. Angelidi, Matthew J. Belanger, Alexander Kokkinos

et al.

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(3), P. 507 - 557

Published: Oct. 21, 2021

Recent insights into the pathophysiologic underlying mechanisms of obesity have led to discovery several promising drug targets and novel therapeutic strategies address global epidemic its comorbidities. Current pharmacologic options for management are largely limited in number modest efficacy/safety profile. Therefore, need safe more efficacious new agents is urgent. Drugs which currently under investigation modulate across a broad range systems tissues, including central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, skeletal muscle. Beyond pharmacotherapeutics, other potential antiobesity being explored, delivery systems, vaccines, modulation gut microbiome, gene therapy. The present review summarizes pathophysiology energy homeostasis, highlights pathways explored effort develop medications interventions but does not cover devices bariatric methods. Emerging alternative approaches targeting these relevant research both animals humans presented detail. Special emphasis given treatment at end development pipeline closer clinic, i.e., compounds that higher chance be added our armamentarium near future. Ultimately, advancements understanding interindividual variation may lead multimodal personalized will result safe, effective sustainable weight loss until root causes problem identified addressed.

Language: Английский

Citations

82
Leptin as a Biomarker of Stress: A Systematic Review and Meta-Analysis DOI Open Access
Jean‐Baptiste Bouillon‐Minois, Marion Trousselard, David Thivel

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(10), P. 3350 - 3350

Published: Sept. 24, 2021

Leptin is a satiety hormone mainly produced by white adipose tissue. Decreasing levels have been described following acute stress.To conduct systematic review and meta-analysis to determine if leptin can be biomarker of stress, with decreasing stress.PubMed, Cochrane Library, Embase, ScienceDirect were searched obtain all articles studying after stress on 15 February 2021. We included reporting before (physical or psychological) conducted random effects (DerSimonian Laird approach). Meta-regressions sensitivity analyses exclusion groups outside the metafunnel.We seven articles-four cohort three case-control studies-(28 groups) from 27,983 putative articles. decreased intervention (effect size = -0.34, 95%CI -0.66 -0.02) compared baseline levels, greater decrease 60 min mean (-0.45, -0.89 -0.01) in normal weight overweight individuals (-0.79, -1.38 -0.21). There was no difference population. Sensitivity demonstrated similar results. Levels sex ratio-i.e., number men/women-(-0.924, -1.58 -0.27) increased (0.039, 0.01 0.07).Leptin stress. Normal-weight women also higher variation suggesting that may implications obesity development response sex-dependent manner.

Language: Английский

Citations

58
Lipid metabolism within the bone micro-environment is closely associated with bone metabolism in physiological and pathophysiological stages DOI Creative Commons
Bo Wang, Heng Wang, Yuancheng Li

et al.

Lipids in Health and Disease, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 7, 2022

Abstract Recent advances in society have resulted the emergence of both hyperlipidemia and obesity as life-threatening conditions people with implications for various types diseases, such cardiovascular diseases cancer. This is further complicated by a global rise aging population, especially menopausal women, who mostly suffer from overweight bone loss simultaneously. Interestingly, clinical observations these women suggest that osteoarthritis may be linked to higher body mass index (BMI), which has led many believe there some degree dysfunction associated obesity. It also common practice outpatient settings encourage patients control their BMI lose weight an attempt mitigate mechanical stress thus reduce pain joint dysfunction. Together, studies show not only organ but critical component metabolism, endocrine functions, calcium metabolism. Numerous demonstrated relationship between metabolic abnormal lipid Previous regarded disorder. However, metabolism been fully elucidated. In this narrative review, data describing close was summarized impact on normal physiology pathophysiology tissues discussed at molecular cellular levels.

Language: Английский

Citations

55
Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets DOI Creative Commons

Yinshuang Chen,

Weipeng Wang, Maria P. Morgan

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 8, 2023

Obesity is a global epidemic and overwhelming evidence indicates that it risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to steatohepatitis (NASH), cirrhosis ultimately HCC. The rising incidence obesity resulting in an increased prevalence NAFLD NASH, subsequently represents increasingly important underlying etiology HCC, particular as other causes HCC such hepatitis infection, are declining due effective treatments vaccines. In this review, we provide comprehensive overview molecular mechanisms cellular signaling pathways involved pathogenesis obesity-associated We summarize preclinical experimental animal models available study features NAFLD/NASH/HCC, non-invasive methods diagnose NAFLD, NASH early-stage Finally, since aggressive tumor with 5-year survival less than 20%, will also discuss novel therapeutic targets ongoing clinical trials.

Language: Английский

Citations

32
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 DOI
Konstantinos Stefanakis, Michail Kokkorakis, Christos S. Mantzoros

et al.

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

Published: Oct. 1, 2024

Language: Английский

Citations

17
Unraveling Adipose Tissue Dysfunction: Molecular Mechanisms, Novel Biomarkers, and Therapeutic Targets for Liver Fat Deposition DOI Creative Commons
Marta Lopez‐Yus,

C. Hörndler,

Sofía Borlán

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 380 - 380

Published: Feb. 22, 2024

Adipose tissue (AT), once considered a mere fat storage organ, is now recognized as dynamic and complex entity crucial for regulating human physiology, including metabolic processes, energy balance, immune responses. It comprises mainly two types: white adipose (WAT) brown (BAT) thermogenesis, with beige adipocytes demonstrating the plasticity of these cells. WAT, beyond lipid storage, involved in various activities, notably lipogenesis lipolysis, critical maintaining homeostasis. also functions an endocrine secreting adipokines that influence metabolic, inflammatory, processes. However, dysfunction especially related to obesity, leads disturbances, inability properly store excess lipids, resulting ectopic deposition organs like liver, contributing non-alcoholic fatty liver disease (NAFLD). This narrative review delves into multifaceted roles its composition, functions, pathophysiology WAT dysfunction. explores diagnostic approaches adipose-related disorders, emphasizing importance accurately assessing AT distribution understanding relationships between compartments health. Furthermore, it discusses therapeutic strategies, innovative therapeutics adipose-derived mesenchymal stem cells (ADMSCs)-based treatments gene therapy, highlighting potential precision medicine targeting obesity associated complications.

Language: Английский

Citations

14