Leptin: a review of its peripheral actions and interactions

Abstract

Following the discovery of leptin in 1994, the scientific and clinical communities have held great hope that manipulation of the leptin axis may lead to the successful treatment of obesity. This hope is not yet dashed; however the role of the leptin axis is now being shown to be ever more complex than was first envisaged. It is now well established that leptin interacts with pathways in the central nervous system and through direct peripheral mechanisms. In this review, we consider the tissues in which leptin is synthesized and the mechanisms which mediate leptin synthesis, the structure of leptin and the knowledge gained from cloning leptin genes in aiding our understanding of the role of leptin in the periphery. The discoveries of expression of leptin receptor isotypes in a wide range of tissues in the body have encouraged investigation of leptin interactions in the periphery. Many of these interactions appear to be direct, however many are also centrally mediated. Discovery of the relative importance of the centrally mediated and peripheral interactions of leptin under different physiological states and the variations between species is beginning to show the complexity of the leptin axis. Leptin appears to have a range of roles as a growth factor in a range of cell types: as be a mediator of energy expenditure; as a permissive factor for puberty; as a signal of metabolic status and modulation between the foetus and the maternal metabolism; and perhaps importantly in all of these interactions, to also interact with other hormonal mediators and regulators of energy status and metabolism such as insulin, glucagon, the insulin-like growth factors, growth hormone and glucocorticoids. Surely, more interactions are yet to be discovered. Leptin appears to act as an endocrine and a paracrine factor and perhaps also as an autocrine factor. Although the complexity of the leptin axis indicates that it is unlikely that effective treatments for obesity will be simply derived, our improving knowledge and understanding of these complex interactions may point the way to the underlying physiology which predisposes some individuals to apparently unregulated weight gain.

A protocol for the isolation and cultivation of brown bear (Ursus arctos) adipocytes

“…Our findings of increasing adipokine concentrations and glycerol release over the course of differentiation indicate commitment to the adipogenic lineage and confirm that brown bear adipocyte differentiation is similar to in vitro adipogenic differentiation in other mammals (Rodriguez et al 2005). Adiponectin production is specific to mature adipocytes (Körner et al 2005) while leptin is produced in several tissues with greatest expression in adipocytes (Margetic et al 2002). Leptin expression was found to increase throughout differentiation (MacDougald et al 1995).…”

Appraisement function of Coenzyme Q10 on body weight changes blood serum biochemical parameters in resembling type 2 diabetic male rats

“…The increased levels of glucose and insulin parameters in fructose fed rats in this study were in relation with elevated leptin level in the same group, compared to control, proved the communication between leptin and insulin secretion in energy homeostasis regulation (Margetic et al, 2002). Blunted insulin release as a result of pancreatic islets chronic exposure to either high glucose or free fatty acid levels (gluco-and lipotoxicity) is associated with a reduction in adenosine tree phosphate synthesis as a result of the inability of β-cells to increase the adenosine tree phosphate levels in response to glucose stimulation (Giovanni et al, 2002).…”

“…Increased oxidative stress is a widely accepted contributor in the expansion and development of diabetes and its complications (Ceriello, 2000;Baynes, 1991). Diabetes is usually accompanied by increased production of free radicals (Baynes andThorpe, 1999, Young et al, 1995) or impaired antioxidant defenses (Halliwell and Gutteridge, 1990;McLennan, 1991). Oxidative stress can increase reactive oxygen species in high free fatty acid condition that mechanism of this oxidative stress depends on increase mitochondrial uncoupling of oxidative phosphorylation and β-oxidation leading to increasing production of reactive oxygen species (Patane et al, 2002).…”

Regulation of lipid accumulation in 3T3-L1 cells: insulin-independent and combined effects of fatty acids and insulin

“…This appears to be the first study to report lipid accumulation in adipocyte lineage cells in response to physiological concentrations of FA, in the absence of the influence of a complex hormone 'cocktail'. Linoleic and oleic acids are considered to be ligands for PPAR-g (Amri et al, 1995;Forman et al, 1997;Margetic et al, 2002;Ferré, 2004;Kokta et al, 2004), however there appear to be no other in vitro adipocyte lineage cell studies, which have investigated PPAR-g expression or lipid accumulation in the absence of insulin. The strategy of the current study was to provide FA in the media at approximately physiological concentrations, as building blocks for lipid synthesis.…”