Pivotal role of leptin in insulin effects

Abstract

The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms) have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow

“…A second possibility is that leptin, acting either directly on adipocytes or via the central nervous system (or both), increases the susceptibility of adipocytes to other apoptosis-inducing factors. A primary candidate in this regard is insulin, because of its critical role in adipocyte survival and the growing body of evidence showing the importance of leptin-insulin interactions (Ceddia et al 1998). Further research into the centrally mediated effects of leptin on bone marrow adipocytes is clearly warranted, but our data indicate that leptin-induced adipocyte apoptosis may be an important mechanism by which the stimulation of leptin receptors in the VMH regulates adipocyte populations in the bone marrow compartment.…”

Insulin and leptin relations in obesity: a multimedia approach

“…• The leptin signaling system with different receptors and pathways: JAK/STAT, IRS, and MAPK systems (9,11,18,23,35,44,45). • Leptin metabolic and physiological effects in the following tissues (9,20,35,45,49): • In the hypothalamus, leptin promotes the expression of anorexigenic peptides (3,11,21,18,28,32,40,44); • In adipose tissue, leptin induces an indirect effect through norepinephrine production by the hypothalamus, stimulating the thermogenesis process in adipocytes (3,7,13,28,37,41,46); • In the pancreas, leptin suppresses basal insulin secretion (7,25,28,34,37,46); and • In muscle, leptin induces fatty acid oxidation and glucose uptake as metabolic responses triggered by AMP-activated protein kinase; stimulates the activity of mitochondrial fatty acid transporters, such as carnitine-palmitoyl transferase (CPT)-I; increases mRNA levels of the transcription factor peroxisome proliferatoractivated receptor-␣␣, a global activator of fatty acid oxidation and uncoupling protein genes; increases the responsiveness of skeletal muscle to insulin by activation of PKB and inhibition of GSK-3; and decreases levels of PKC, which has been implicated in the pathogenesis of lipid-induced insulin (7,37,19,30,31,33,…”

Genetic variations in the leptin gene associated with growth and carcass traits in Nellore cattle

“…In bovines, this gene is found in chromosome 4 (4q32) and is 16,735 Kb, with 3 exons and 2 introns (Taniguchi et al, 2002). Its final product is leptin protein (167 amino acids) of hormonal origin, which has an autocrine action that inhibits insulin-stimulated glucose uptake and reduces lipogenesis in the adipose tissue (Ceddia et al, 1998).…”