The challenge of treating obesity: the endocannabinoid system as a potential target.

Obesity and cardiometabolic risk, or the metabolic syndrome, continue to be major public health concerns. To date, treatment with lifestyle and pharmacotherapy interventions has resulted in limited efficacy in reversing the upward trend in this present-day health crisis. Research reveals that a modest 5% to 10% weight loss results in substantial improvement in health. While obtaining modest weight loss is often achievable, maintaining lost weight is challenging. Research has recently improved our understanding of several endogenous pathways that influence body weight regulation and disease risk. The endocannabinoid system has been found to regulate appetite and energy expenditure, as well as lipid and glucose metabolism. Interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development is an area of interest and research. This article reviews the mechanisms by which the endocannabinoid system is believed to influence body weight regulation and cardiometabolic risk factors, as well as the results of clinical trials investigating the safety and efficacy of a selective cannabinoid-1 receptor antagonist (rimonabant). Clinical trials investigating rimonabant treatment resulted in substantial reductions in body weight and markers for cardiometabolic risk in study participants. However, increases in adverse events were reported in the drug-treated group. Data regarding long-term benefit and adverse events from rimonabant treatment are being collected in several ongoing clinical trials. Rimonabant is currently available in 42 countries, but has not received United States Food and Drug Administration approval. Food and nutrition professionals play a pivotal role in tackling the current obesity crisis; it is essential that they understand the many physiological mechanisms regulating body weight. Emerging research data reveals pathways that influence appetite and energy metabolism, and this knowledge may form the foundation for new clinical treatment options for obese individuals.

Cannabinoid-1 receptor blockade in cardiometabolic risk reduction: efficacy.

Intra-abdominal fat mass, or central adiposity, and cardiovascular risk are strongly correlated. Adipose tissue is an endocrine organ that secretes hormones and cytokines influencing appetite, energy metabolism, and atherosclerosis. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend that if dietary and lifestyle interventions fail to produce favorable outcomes in individuals with a body mass index >27 and weight-related comorbidities, as well as those with a body mass index >30, treatment plans may include weight loss medication. The endocannabinoid system has recently emerged as a viable target for the pharmacologic treatment of obesity and cardiometabolic risk factors. This article provides an in-depth review of efficacy results from clinical trials of rimonabant, a selective cannabinoid-1 receptor. (Recently, an FDA Advisory Committee recommended a delay in the approval of rimonabant because of safety issues that need to be addressed in further studies.) Compared with placebo, rimonabant 20 mg significantly decreased body weight and waist circumference measurements. In addition, rimonabant was associated with favorable changes in several other cardiometabolic risk factors, including significant increases in serum levels of high-density lipoprotein cholesterol and adiponectin, as well as reductions in serum levels of triglycerides, small, dense low-density lipoprotein particles, C-reactive protein, insulin resistance, and glycosylated hemoglobin.

Obesity with Comorbid Stress Urinary Incontinence in Women: A Narrative Review to Inform Dietetics Practice.

Stress urinary incontinence (SUI) is a common problem among women; clinical treatment guidelines include weight reduction as a strategy for controlling urinary leakage. The purpose of this review was to gather evidence on the association between obesity and SUI and to ascertain whether there are any special considerations for implementing medical nutrition therapy with community-dwelling, obese, adult females with comorbid SUI. Five key findings emerged: epidemiologic studies consistently report statistically significant associations between obesity and SUI, randomized control trials found that weight loss appears to ameliorate SUI symptoms, the SUI-activity link may affect weight management, there is a potential interplay between SUI and the obesity-sleep connection, and dietary components are associated with the exacerbation of urinary symptoms. The pathogenesis of SUI and obesity-related contributions to urinary leakage is included in the introductory discussion. Lastly, insights on special considerations for implementing nutrition interventions with this population are offered.

When prevention fails: obesity treatment strategies.

The obesity epidemic has resulted in increasingly urgent calls for large-scale prevention strategies. Meanwhile, effective treatment approaches that result in sustainable weight loss are needed to attenuate the cardiometabolic risks that may lead to comorbid illnesses and early mortality. Public education efforts geared toward those afflicted with obesity should emphasize that a relatively modest reduction in body weight dramatically reduces disease risk, thereby improving overall long-term health. Setting realistic weight loss goals with patients should reduce the overwhelming frustration often associated with the belief that large amounts of weight loss are needed for improved health. This misconception often impedes overweight and obese individuals from seeking treatment. Effective strategies are available to help overweight and obese individuals achieve reasonable weight loss goals. Important challenges exist in preventing weight regain following weight loss intervention. Studies are underway to identify new therapeutic strategies to effectively reduce weight, as well as to provide long-term data on successful weight loss maintenance strategies.

Cardiovascular disease in obesity: A review of related risk factors and risk-reduction strategies.

Cardiovascular disease (CVD) is the number one cause of mortality in men and women. Currently, two thirds of US adults are overweight or obese. CVD and obesity are closely linked and together take a substantial toll on the health of individuals and the community. It is creating a growing burden on public health and financial difficulties in both personal and institutional funding of health care. A review of recent scientific literature reveals that modest weight loss of 5% to 10% ameliorates cardiometabolic risk factors and improves health outcomes. To date, successful weight-loss interventions have been elusive. The choice of weight-loss medications is limited, and the risks of surgical intervention demand that this option be reserved for those patients with extreme obesity. Research has elucidated an improved understanding of the mechanisms leading to obesity and disease. The potential role of hormones, such as leptin and adiponectin, in altering metabolism and vascular disease is better understood. The endocannabinoid system is now recognized as a potentially viable pathway to modulate appetite and energy, lipid, and glucose metabolism.