Interaction Between Exercise and Leptin in the Treatment of Obesity

Abstract

Recent data indicate that roughly 32% of the U.S. population is obese and an additional 34% is overweight (1). Considering the physical, psychological, and physiological complications associated with obesity, developing approaches to reduce these numbers is of critical importance. The identification of leptin as a hormonal link between energy stores and the brain inspired a renewed focus on the study of energy balance and contributed to the description of a neuronal network that mediates the metabolic regulation of feeding behavior, reproduction, glucose homeostasis, immune function, bone formation, lipid metabolism, etc. But for all its promise, much of the initial enthusiasm over leptin has waned with the realization that obese individuals respond rather poorly to leptin treatment and manifest a syndrome of leptin resistance. Although leptin may not be the anti-obesity treatment initially hoped for, there may yet be life to the leptin story. Just as progress has been made in defining and overcoming insulin resistance, considerable effort has focused on developing approaches to overcome leptin resistance. In this issue of Diabetes, Shapiro et al.(2) provide evidence that modest exercise synergizes with leptin treatment to markedly reduce body weight in individuals made obese by a high-fat diet, even though neither reduce body weight alone.The importance of leptin in energy balance is illustrated by the extreme obese phenotype induced by leptin deficiency, and by the dramatic reduction in food intake and body weight that occurs upon treatment of this condition with leptin. While leptin levels are closely matched to body adiposity at steady state, negative energy balance produces a fall in leptin levels that is more rapid than the change in body adiposity. Preventing this fall is sufficient to attenuate many of the physiological events associated with negative energy balance, and it is widely agreed that leptin is a critical signal of weight loss. However, is the opposite also true? That is, does increased leptin serve as a signal of positive energy balance? Though the answer to this question is unclear, there is increasing evidence that enhancing leptin sensitivity produces a lean, obesity-resistant phenotype (3-6). These observations therefore suggest that leptin may indeed act to prevent weight gain, and that enhancing leptin sensitivity might be beneficial in the fight against obesity.The work by Shapiro et al. (2) builds upon previous experiments by the Scarpace group. This work demonstrates not only that prolonged leptin overexpression is ineffective at reducing body weight in obese rats, but also that chronic leptin treatment actually worsens diet-induced obesity (2,7). Far from providing a cure, chronic hyperleptinemia might actually contribute to obesity. But why would increased leptin levels make matters worse? First, it is important to note that the effect only occurs in animals on a high-fat diet, as those rats on a low-fat diet exhibited the expected leptin-induced reduction in body weight. Second, i...

Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice

“…While leptin levels are closely matched to body adiposity, increased energy expenditure and reduced triglycerides in serum [56] with EPA9 and 18 may explain the reduced leptin levels without significantly reducing BW and adiposity compared to HF, as the negative energy balance produces a fall in the leptin level, which is more rapid than change in adiposity [57]. Additionally, EPA9 significantly decreased fasting insulin, leptin, and triglyceride levels and significantly increased energy expenditure and oxygen consumption compared to HF which is comparable to healthy obese subjects criteria [58].…”

Antiobesity Effects of Human Soluble Leptin in Mice Nourished With a High-Fat/High Fructose Diet

“…Leptin is mainly produced in white adipose tissue, followed by brown adipose tissue, placenta, ovaries, skeletal muscle, stomach, mammary epithelial cells, bone marrow, pituitary and liver (Prins, 2002;Masuzaki et al, 1997;Paz-Filho et al, 2010). The effect of Leptin in energy balance is evidenced by the extreme obese phenotype caused by Leptin scarcity and by the dramatic decrease in food intake and body weight that occurs upon treatment of this condition with Leptin administration (Morrison, 2008). Even though, obese individuals usually show increased levels of Leptin in serum and respond unsuccessfully to Leptin treatment (Bence et al, 2006).…”