Pharmacotherapy of Obesity - Benefit, Bias and Hyperbole

Abstract

Overweight and obesity, if sustained, are serious medical problems reaching an epidemic proportion. It is estimated that over 55% of the adult population is affected by overweight and obesity. Both overweight and obesity put these individuals at a high risk for the development of insulin resistance, hypertension, dyslipidemia, type 2 diabetes and coronary heart disease. A weight loss of between 5% and 10% of the initial body weight has been shown to greatly reduce these health risks associated with overweight and obesity. Typically, the first-line clinical strategy for weight loss is a combination of supervised diet, exercise and behavior modification. Although life style modification can exert beneficial effects in overweighed and obese individuals, it is difficult to achieve and maintain weight losses solely by life style change. Anti-obesity drugs may be used in obese patients (BMI of 30 or greater), or overweight patients with established comorbidities (BMI > 27), where dietary and lifestyle modifications are unsuccessful in achieving a 10% weight reduction following at least three months of the supervised care. Current anti-obesity drug therapy is geared towards reducing energy/food intake via actions on either gastrointestinal system or the central control of appetite and feeding. A thorough understanding of the molecular pathways involved in weight gain and appetite suppression should help for a better drug design and development. This mini review will focus on the molecular mechanisms and currently available pharmacotherapeutic interventions in overweight and obesity.

Proteomic profile of visceral adipose tissues between low-fat diet-fed obesity-resistant and obesity-prone C57BL/6 mice

“…Introduction obesity, with its devastating implications for overall health, is a serious medical problem now reaching epidemic proportions worldwide (1). it is associated with an increased risk of numerous comorbidities, such as type 2 diabetes, metabolic syndrome, hypertension, cardiovascular diseases and osteoarthritis (2).…”

“…However, certain individuals are still rendered obese even though they are subjected to low-fat or normal-fat diets. currently, the approach for treating obesity primarily involves caloric restriction, physical exercise and use of antiobesity drugs (1). The study of susceptibility to diet-induced obesity may be useful for identifying potential targets for preventing the development of obesity.…”

Metabolic Syndrome, Obesity, and Diabetes

“…However, there are subsets of individuals who are unable to lose weight with lifestyle modification. There are pharmacological (Nair and Ren, 2009) and surgical interventions (Smith et al, 2008) available to assist with weight loss in the severely obese or in those with obesity-related complications. However, it is difficult to know if these interventions can successfully correct the programmed metabolic imbalances that lead to overnutrition and the behaviors that contributed to the problem in the first place.…”

Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’ and metabolic disease

“…Strictly from a health standpoint, even a 5% weight loss may improve the adipose tissue pathogenic responses characteristic of adiposopathy [29]. Thus, even a mild-to-modest weight loss of 5-10% in overweight patients may help prevent the onset of, or provide clinically meaningful therapeutic benefits in the treatment of, Type 2 diabetes mellitus, high blood pressure and/or dyslipidemia [30,31]. The practical implication is that the focus of any weight loss investigational agent should have the following caveat:…”