Current and Future Drug Targets in Weight Management

Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed

Total and specific dietary polyphenol intakes and 6-year anthropometric changes in a middle-aged general population cohort

International audienceBACKGROUND:Dietary polyphenols are suggested anti-obesogenic agents. Prospective evidence in general populations of an association between polyphenol intakes and anthropometry is lacking.OBJECTIVE:To assess the associations between dietary polyphenol intakes and changes in body mass index (BMI) and waist circumference (WC) over a 6-year period.METHODS:Individual intakes of 264 different polyphenols (mg/day) were estimated using the Phenol-Explorer database and the mean of 6-17 24-h dietary records collected in 1994-1996. BMI in kg/m2 and WC in cm were measured in 1995-1996, 1998-1999 and 2001-2002. Linear mixed effect models allowed for the assessment of longitudinal associations between energy adjusted quartiles of total polyphenol intake as well as intake of 15 polyphenol classes and changes of these respective polyphenol classes in anthropometry over the 6 years of follow-up. Adjustment variables included sex, age, socio-economic status, lifestyle, dietary intakes and health status.RESULTS:Participants in the highest quartile of intake of flavanones (BMI change: -0.28 (-0.43; -0.13), P=0.009), flavones (BMI change: -0.29 (-0.44; -0.14), P=0.008), and lignans (BMI change: -0.28 (-1.63; -0.09), P=0.01) experienced a less notable increase in BMI over time compared to their counterparts in the bottom quartile of intake of the respective polyphenol classes. Participants in the highest quartile of intake of flavanones (WC change: -1.39 (-2.02; -0.92), P=0.001), flavones (WC change: -1.57 (-2.32; -0.92), P=0.001), hydroxycinnamic acids (WC change: -1.27 (-1.92; -0.63), P=0.01), lignans (WC change: -1.16 (-1.80; -0.51), P=0.006) and total polyphenol intake (WC change: -1.39 (-2.05; -0.74), P=0.001) experienced a less notable increase in WC over time compared to their counterparts in the bottom quartile of intake of the respective polyphenols.CONCLUSIONS:Dietary polyphenol intakes may help reduce weight gain over time in the general population. This could have important public health implications because moderate increases in BMI and WC over time have been shown to increase disease risk