Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Mechanisms of leptin resistance in obesity (#130)

Eglantine Balland 1 , Vincent Prevet 2 , Michael Cowley 1
  1. Monash Obesity and Diabetes Institute, Physiology Department, Monash University, Clayton, VIC, Australia
  2. Jean-Pierre Aubert Research Center, Institut National de la Santé et de la Recherche Médicale, Lille, France

Obesity is reaching an epidemic prevalence in western countries, associated with complications such as cardio-vascular diseases, cancer and type 2 diabetes. The body weight of an individual is determined by the value of its energy balance. In this context, obesity is defined by a chronically positive energy balance resulting in fat mass increase. Leptin is a hormone synthesized by adipose tissue responsible for the maintenance of energy homeostasis and the control of reproduction. It also has been established that leptin play an important role in the regulation of glucose homeostasis.
Most of obese individuals exhibit a highly increased leptin level in serum, directly linked to their level of adiposity. However, elevated leptin level has no effect on body weight of obese individuals, this observation led to the establishment of leptin resistance concept defined by the incapacity of obese individuals (humans or animals) to respond to an elevated endogenous or exogenous leptin level.
To date, three mechanisms explaining the cause of leptin resistance has been identified: First, an alteration of leptin transport from the blood to the hypothalamus, a critical site for leptin actions. Secondly, a role played by astrocytes proliferation and inflammation affecting the environment of leptin-sensitive neurons. Lastly, the suppression of LepRb-associated signaling pathways caused by the increase of negative feed-back inhibitors such as SOCS3 and phosphatases.
Here we propose to discuss and bring some new insight to each of these mechanisms responsible for leptin resistance.