The Association Between Triglyceride and Leptin Levels in Obese Subjects Following a Low-Carbohydrate or Low-Fat Diet

Obesity has been cited as the second leading preventable cause of death in the United States. Studies have determined that at risk overweight and obese individuals have high circulating levels of leptin indicative of leptin resistance as well as elevated levels of plasma triglycerides. Postulates have been formed that link elevated levels of triglycerides with the inhibition of leptin across the blood-brain barrier. If a method of lowering triglycerides is achieved, leptin should be able to cross the blood-brain barrier and reach the ypothalamus, thus regulating body weight through a decrease in appetite and increase in energy expenditure. The primary aim of this study was to compare the effects of both carbohydrate and fat restricted diets on plasma triglycerides and leptin concentrations in overweight and obese subjects with hypertriglyceridemia. Forty subjects were randomly assigned to either the low carbohydrate or low fat diet group for a 12 wk period. Plasma triglyceride and leptin concentrations in the blood were analyzed before and after the 12 wk period to assess diet-induced changes. Both groups had a significant reduction in body weight, though the effect was much greater in the carbohydrate restricted diet group. Fasting and postprandial plasma triglycerides also decreased to a greater extent in the low carbohydrate diet group. Similarly, leptin levels decreased to a greater extent in the carbohydrate restricted diet group. The changes in leptin levels were directly related to the changes in both fasting and postprandial triglyceride levels. The results from this study provide preliminary evidence of diet-induced triglyceride reductions as an underlying mechanism in lowering plasma leptin and improving leptin sensitivity. Further, they provide evidence that an increase in triglyceride levels is at least partially responsible for leptin resistance and reduced leptin sensitivity in obese hypertriglyceridemic individuals. This novel discovery is important as it raises the possibility that other methods of lowering triglycerides may improve the efficiency of leptin transport and ultimately improve fat metabolism in overweight and obese individuals.

AM 6545: A Novel Peripheral CB1 Antagonist

Obesity and other related metabolic disorders are a common problem in the United States. Consequently, several drug therapies have been developed in an attempt to address this problem. Many older appetite suppressants, such as amphetamines, were dangerous and potentially addictive. For the last few years, the endocannabinoid system was investigated as a potential target for appetite suppression. Unfortunately, early cannabinoid CB1 antagonists came with an unacceptable side effect profile of their own, which is largely due to central actions of these drugs. In an attempt to reduce the side effect profile, researchers are investigating peripherally acting cannabinoid antagonists, which do not penetrate the blood brain barrier. This study investigated AM 6545, a novel peripheral cannabinoid antagonist, for its effects on food reinforced instrumental behavior. In the end, the results indicated that AM6545 produced a dose-related suppression of lever pressing for food reinforcement.