Insulin and leptin are classically regarded as peptide hormones that play key roles in metabolism. In actuality, they serve several functions in both the periphery and central nervous system (CNS). Likewise, insulin and leptin resistance can occur both peripherally and centrally. Metabolic disorders such as diabetes and obesity share several key features including insulin and leptin resistance. While the peripheral effects of these disorders are well-known (i.e. cardiovascular disease, hypertension, stroke, dyslipidemia, etc.), the CNS complications of leptin and insulin resistance have come into sharper focus. Both preclinical and clinical findings have indicated that insulin and leptin resistance are associated with cognitive deficits and neuropsychiatric diseases such as depression. Importantly, these studies also suggest that these deficits in neuroplasticity can be reversed by restoration of insulin and leptin sensitivity. In view of these observations, this review will describe, in detail, the peripheral and central functions of insulin and leptin and explain the role of insulin and leptin resistance in various metabolic disorders, cognition, and neuropsychiatric diseases.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108877 | DOI Listing |
Brain Behav Immun Health
February 2025
Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
Purpose: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly recognized for its strong association with chronic inflammation. Adipose tissue functions as an endocrine organ and can secrete inflammatory cytokines to mediate inflammation. However, its involvement in ASD-related inflammation remains unclear.
View Article and Find Full Text PDFDiabetes 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.
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.
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 PDFBiomed Pharmacother
January 2025
Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Republic of Korea; Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Republic of Korea. Electronic address:
Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders.
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