Bray, G. A. Lifestyle and pharmacological approaches to weight loss: efficacy and safety. J. Clin. Endocrinol. Metab. 93, S81-S88

Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 11/2008; 93(11 Suppl 1):S81-8. DOI: 10.1210/jc.2008-1294
Source: PubMed


Obesity results from a prolonged small positive energy balance, and its treatment needs to reverse this imbalance.
Citations retrieved from PubMed and The Handbook of Obesity 2008 were selected to illustrate the points.
Many different diets have been tried to treat obesity, and weight loss occurs with all of them. There is currently no evidence that clearly supports a superiority of one macronutrient composition for diets used for weight loss. The principal effect seems to be the degree of adherence to the prescribed calorie reduction. Lifestyle strategies to modify eating behavior can be used in individual counseling sessions or in groups, both of which are important in helping patients modify their patterns of eating. Physical activity is particularly important in helping patients maintain a weight loss once achieved and is less valuable for weight loss itself. Food intake is controlled through many different mechanisms, but only a few drugs have been developed that tap these mechanisms. Orlistat, which blocks intestinal lipase, is one; sibutramine, a serotonin-norepinephrine reuptake inhibitor, is a second. Surgical approaches provide the most dramatic weight loss and have been demonstrated to reduce long-term mortality and reduce the incidence of diabetes.
Weight loss can be achieved by many methods, but the surgical procedures appear to be the most durable.

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    • "Obesity, characterized by excessive fat accumulation in the form of triglycerides (TG) in adipose tissue and ectopic TG deposition in other organs, is a primary risk factor for type 2 diabetes, cardiovascular diseases, and other comorbidities. Current pharmacological treatments are inadequate for weight loss [1]. Thus, a more detailed knowledge of pathways that influence energy homeostasis is necessary for the development of safe, more effective obesity and diabetes therapies. "
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    ABSTRACT: Diacylglycerol acyltransferase-1 (DGAT1) is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4) inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.
    PLoS ONE 01/2013; 8(1):e54480. DOI:10.1371/journal.pone.0054480 · 3.23 Impact Factor
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    • "Theoretically, improving NAFLD via weight loss is an ideal approach in obese or overweight people because other complications are simultaneously ameliorated. Of several commonly used antiobesity medications [134], orlistat and sibutramine are available for long-term prescription [135, 136]. Orlistat inhibits dietary triglyceride hydrolysis in the gut, occasionally with mild gastrointestinal symptoms, resulting in a substantial decrease in fat absorption. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.
    12/2012; 2012(8):950693. DOI:10.1155/2012/950693
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    • "There are several risks associated with the pharmacologic and surgical interventions of obesity, suggesting that a dietary intervention maybe the safest and most cost-effective option for those who are moderately obese [5,20–22]. There are many dietary strategies that have been shown to affect energy balance in a manner that results in successful weight loss [23] [24]. The pomegranate (Punica granatum L.) is a deciduous shrub cultivated throughout Iran, India, the Mediterranean countries, Malaysia, and tropical Africa and to some extent in the United States [25] [26]. "
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    ABSTRACT: Obesity represents a rapidly growing threat to the health of populations in an increasing number of countries. Diet intervention has been proposed as one of the strategies for weight loss and weight maintenance. Traditionally, the pomegranate, including its roots, tree bark, fruit juice, leaves, and flowers, has been used to treat some conditions such as diarrhea, hemorrhage, acidosis, and microbial infections. Pomegranate extracts have been found to have strong anti-inflammatory, antioxidant, and even antitumor properties in vivo and in vitro. More recently, positive effects on fat reduction have been shown using the pomegranate and its extracts. Many of the beneficial effects are related to the presence of anthocyanins, tannins, and very high levels of antioxidants, including polyphenols and flavonoids. Many studies have explored the effects of the pomegranate in obesity, and various mechanisms have been proposed as to how these different extracts help in fat reduction. This article provides an overview of the work done addressing the potential benefits of the pomegranate on obesity and assesses the efficacy of intervention by means of the pomegranate and its extracts. Human studies in this field are still limited and need more attention that would help in understanding the preventive and protective roles pomegranate extracts have on obesity.
    Nutrition 02/2012; 28(6):595-604. DOI:10.1016/j.nut.2011.11.013 · 2.93 Impact Factor
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