Possible Integrative Actions of Leptin and Insulin Signaling in the Hypothalamus Targeting Energy Homeostasis - PubMed (original) (raw)

Review

Possible Integrative Actions of Leptin and Insulin Signaling in the Hypothalamus Targeting Energy Homeostasis

Mina Thon et al. Front Endocrinol (Lausanne). 2016.

Abstract

Obesity has emerged as one of the most burdensome conditions in modern society. In this context, understanding the mechanisms controlling food intake is critical. At present, the adipocyte-derived hormone leptin and the pancreatic β-cell-derived hormone insulin are considered the principal anorexigenic hormones. Although leptin and insulin signal transduction pathways are distinct, their regulation of body weight maintenance is concerted. Resistance to the central actions of leptin or insulin is linked to the emergence of obesity and diabetes mellitus. A growing body of evidence suggests a convergence of leptin and insulin intracellular signaling at the insulin-receptor-substrate-phosphatidylinositol-3-kinase level. Moreover, numerous factors mediating the pathophysiology of leptin resistance, a hallmark of obesity, such as endoplasmic reticulum stress, protein tyrosine phosphatase 1B, and suppressor of cytokine signaling 3 also contribute to insulin resistance. Recent studies have also indicated that insulin potentiates leptin-induced signaling. Thus, a greater understanding of the overlapping functions of leptin and insulin in the central nervous system is vital to understand the associated physiological and pathophysiological states. This mini-review focuses on the cross talk and integrative signaling of leptin and insulin in the regulation of energy homeostasis in the brain.

Keywords: GRP78; endoplasmic reticulum stress; food intake; insulin; leptin; leptin resistance.

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Figures

Figure 1

Figure 1

Structure of leptin receptor isoforms. Six different spliced isoforms of the leptin receptors (ObR) have been documented as ObRa–ObRf. All the isoforms share identical extracellular binding domain. ObRb possesses the longest intracellular domain, which is important for leptin signaling.

Figure 2

Figure 2

A diagrammatic representation of the integration of leptin and insulin signals in the regulation of energy homeostasis in the central nervous system. Adipocyte-derived hormone leptin and pancreatic hormone insulin bind to leptin receptors (ObRb) and insulin receptors (IRs), respectively, in the hypothalamus. Leptin and insulin regulate the expression of proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the hypothalamus via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to suppress food intake.

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