The Adipose Tissue, Leptin Signaling, and Adiponectin in Obesity and Type 2 Diabetes Mellitus
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Abstract
The global rise in obesity represents a major public health challenge and is closely associated with the increasing prevalence of metabolic syndrome and type 2 diabetes mellitus (T2DM). Obesity is characterized by excessive accumulation of adipose tissue, which contributes to the development of insulin resistance, chronic low-grade inflammation, and multiple metabolic complications. T2DM accounts for the majority of diabetes cases and is a complex metabolic disorder involving both impaired insulin action and β-cell dysfunction. Its growing incidence parallels the increasing rates of obesity worldwide.
Adipose tissue is now recognized as a metabolically active endocrine organ rather than a passive energy reservoir. It plays a central role in energy homeostasis through lipid storage and the secretion of adipokines, including leptin and adiponectin, which are critical regulators of metabolic processes. Leptin is a key hormone involved in appetite regulation and energy expenditure, acting primarily through hypothalamic signaling pathways such as JAK/STAT, PI3K/Akt, MAPK, and AMPK. However, in obesity, elevated leptin levels fail to exert their expected physiological effects due to the development of leptin resistance, which is associated with disruptions in intracellular signaling, inflammation, and cellular stress responses.
In contrast, adiponectin exerts insulin-sensitizing, anti-inflammatory, and anti-atherogenic effects, primarily through activation of metabolic signaling pathways that enhance glucose utilization and fatty acid oxidation. Its circulating levels are inversely correlated with adiposity and are reduced in obesity and T2DM, contributing to metabolic dysregulation.
Understanding the molecular interplay between adipose tissue, leptin signaling, and adiponectin is essential for elucidating the pathogenesis of obesity-related metabolic disorders and for developing targeted therapeutic strategies.
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