Metabolism leptin effect

Adipocytes have an important secretory function. Numerous factors (collectively termed adipokines or adipocytokines), mostly peptides but also eicosanoids are produced by preadipocytes and mature adipocytes (Table 9.3). Some of these factors act in an autocrine or paracrine fashion to regulate adipogenesis, that is differentiation and maturation of adipocytes themselves, whilst others, notably, leptin, adiponectin and some cytokines act in truly endocrine way, having effects on the brain, endothelial cells, liver and skeletal muscle. Disturbance in secretion from adipocytes is associated with eating disorders and metabolic syndrome. 

Other hormones Thyroxine has long been known to increase metabolic rate, although the mechanism for this effect is not totally clear (Silvestri et al. 2005). More recently the hormone leptin, which is secreted by adipose tissue, has also been found to increase the metabolic rate. This effect of leptin is considered to play a role in controlling the amount of adipose tissue in the body, although this is a controversial subject (Chapter 12). 

The answer is A. Recent research has revealed that excess visceral fat deposits secrete several factors that have direct effects on the brain as well as directly on muscle to produce peripheral insulin resistance. Some of these newly identified factors are leptin, re-sistin, and adiponectin, whose mechanisms of action are still under active investigation. Death of pancreatic beta cells is a hallmark feature of type 1 diabetes and may occur only in very advanced stages of type 2 diabetes. Excess adipose in the thighs and buttocks does not contribute as strongly to insulin resistance as does visceral fat, presumably due to a lower level of endocrine activity of such fat depots. Dysfunction of liver lipid metabolism is more a consequence of excess activity of adipose than a cause of insulin resistance. A sedentary lifestyle contributes to build-up of excess fat stores but does not act directly to induce insulin resistance. 

Overton JM, William TD, Chambers JB, Rashotte ME. Central leptin infusion attenuates the cardiovascular and metabolic effects of fasting in rats. Hypertension 2001 37 663-669. 

Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O Rahilly S (2002) Beneficial effects of leptin on obesity, T cellhyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110 1093-1103... 

Nagao, K., Inoue, N., Ujino, Y., Higa, K., Shirouchi, B., Wang, Y. M., and Yanagita, T. 2008. Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice. Lipids Health Dis., 7, 8. 

Recombinant human leptin was recently cloned (8) and expressed in E. coli, and demonstrated to effectively regulate adiposity in mice through modulation of appetite and metabolism (9, 10). The molecule contains four methionine residues at positions 1, 54, 68, and 136. In this paper, we report the separation and characterization of three norleucine-incorporated recombinant human leptins which were uniformly labeled with 15n isotope or double labeled with and isotopes. The extent of incorporation at each methionine residue can be determined by reverse-phase HPLC and amino acid analysis methods. The norleucine incorporation was observed preferentially occurring at the internal Met residues. 

FIGURE 24.4 Leptin has multiple effects on metabolism. It affects the brain, lowering appetite. It also inactivates acetyl-CoA carboxylase (ACC). Reduced activity of ACC leads to a reduction in malonyl-CoA, which stimulates fatty-acid oxidation and reduces fatty-acid synthesis. (From Nature, Vol. 

Adipose tissue is viewed not simply as a passive lipid storage depot but instead as a highly active metabolic tissue, which secretes numerous products that affect insulin resistance either through a traditional (circulating) hormonal effect, or through local effects on the adipocyte. The term adipokines has been used to describe the numerous adipocyte secretory proteins, which include TNFa, IL-6, leptin, PAI-1, resistin, and adiponectin. 

On the other hand, hyperinsulinemic effects of CLA have been found in studies with lean models, particularly in mice. As discussed before, these effects are likely linked to the vast decrease of adipose tissue. The adipose tissue is the source for many factors that influence lipid metabolism, such as leptin, adiponectin, CLUT4, and TNFa. Due to the extensive decrease in adipose tissue by CLA in both lean and obese mice, a simultaneous modulation of these factors may occur. Tsuboyama-Kasaoka et al. demonstrated that leptin infusion in CLA-fed lean mice reduced insulin levels, and also reduced the increase in liver weight and vacuolization found after CLA intake (7). 

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