Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates energy expenditure through interactions with neuronal pathways in the brain, particularly pathways involving the hypothalamus. Intact functioning of the leptin route is required for body weight and energy homeostasis. Given its function, the discovery of leptin increased expectations for the treatment of obesity. However, most obese individuals and subjects with a predisposition to regain weight after losing it have leptin concentrations than lean individuals, but despite the anorexigenic function of this hormone, appetite is not effectively suppressed in these individuals. This phenomenon has been deemed leptin resistance and could be the result of impairments at a number of levels in the leptin signalling pathway, including reduced access of the hormone to its receptor due to changes in receptor expression or changes in post-receptor signal transduction. Epigenetic regulation of the leptin signalling circuit could be a potential mechanism of leptin function disturbance. This review discusses the molecular mechanisms, particularly the epigenetic regulation mechanisms, involved in leptin resistance associated with obesity and the therapeutic potential of these molecular mechanisms in the battle against the obesity pandemic.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.lfs.2015.05.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Leptin increases chemosensitivity by inhibiting in colorectal cancer cells.
J Gastrointest Oncol
December 2024
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.
Background: Chemoresistance is a major cause of treatment failure in advanced colorectal cancer (CRC), severely impacting patient survival and quality of life. While conventional chemotherapy regimens can somewhat control tumor progression, their effectiveness is frequently compromised by the development of drug resistance in cancer cells. The aim of this study is to verify and elucidate the specific mechanisms by which leptin enhances chemosensitivity in CRC, providing valuable insights for the development of new combination chemotherapy options.
View Article and Find Full Text PDFMaternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring.
Cell Metab
January 2025
Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Center for Preventive Medicine, Keio University, Tokyo, Japan. Electronic address:
Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation.
View Article and Find Full Text PDFEarly Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort.
Diabetes Metab Res Rev
January 2025
Division of Research, Kaiser Permanente Northern California, Pleasanton, California, USA.
Aims: Gestational diabetes mellitus (GDM) poses a significant risk for developing type 2 diabetes mellitus (T2D) and exhibits heterogeneity. However, understanding the link between different types of post-GDM individuals without diabetes and their progression to T2D is crucial to advance personalised medicine approaches.
Materials And Methods: We employed a discovery-based unsupervised machine learning clustering method to generate clustering models for analysing metabolomics, clinical, and biochemical datasets.
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 Obes Metab
January 2025
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Background: Medications targeting the leptin and Apolipoprotein CIII (APOC3) pathways are currently under development for the treatment of hypertriglyceridaemia. Given that both pathways are implicated in triglyceride regulation, it is unknown whether they function independently or interact under physiological conditions and under acute or long-term energy deficiency.
Methods: APOC3 levels and their association with circulating lipids and lipoproteins were evaluated in the context of two randomised controlled studies.
Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.
J Transl Med
January 2025
Metabolism and Investigation Unit, Maimonides Institute of Biomedicine Research of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.
Background: Perinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!