New Vistas for the Treatment of Obesity: Turning the Tide Against the Leading Cause of Morbidity and Cardiovascular Mortality in the Developed World

ArticleinReviews in cardiovascular medicine 14(1):20-40 · May 2013with42 Reads
DOI: 10.3909/ricm0682 · Source: PubMed
Abstract
Excess adiposity and obesity are the root cause of at least 27 diseases that cause considerable lifelong morbidity and, in many scenarios, eventual cardiovascular mortality. The human body has the ability to increase the number and size of its adipocytes by approximately 10-fold over the course of a lifetime. As fat mass increases, its blood supply, supporting cells, tissue structure, and local and systemic hormonal control also increase. This results in excess adiposity, leading to progressive obesity and the resistance to weight-loss attempts. There have been numerous trials of food diets combined with exercise that, in general, have a 50% dropout rate at 1 year and lead to very modest (∼ 5%) reductions in body weight. Thus, many with obesity require interventions beyond casual diet and exercise advice. Meal replacement diets and bariatric surgery offer considerably greater degrees of weight loss, but both can be plagued by weight regain. Because the ability to control food urges has been shown to be a key psychological factor for success, medicinal approaches that work in this domain are attractive adjuncts to diet, exercise, and weight-loss surgery. This article reviews the emerging role of medical therapy in the treatment of excess adiposity with the goal of reducing comorbidities and possibly improving cardiovascular survival.
    • "Obesity is a major risk factor for the development of type II diabetes (T2DM), cardiovascular diseases, and some types of cancer12345. Searching for more efficient and safe approaches to prevent and treat obesity has been the focus of intensive research. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: We have shown previously that microvesicle (MV)-delivered miR-130b (miR-130b-MV) is able to target PPAR-γ and subsequently reduce the lipid accumulation in vitro. However, the in vivo effect of miR-130b on fat deposition and glucose homeostasis remains unknown. Results: Three-week-old C57BL/6 mice were fed a high-fat diet for 8 weeks and then intravenously injected with MV-packaged scrambled control microRNA (miRNA) or miR-130b every other day for 10 days. Glucose tolerance test was performed and body weight, epididymal fat weight, as well as the expression of lipid metabolic genes were determined. We showed that mice fed on high-fat diet for 8 weeks demonstrated significantly higher body weight, elevated blood glucose and impaired glucose tolerance. miR-130b-MV injection significantly reduced body weight and epididymal fat weight and partly restored glucose tolerance. miR-130b expression was significantly increased in the epididymal fat after miR-130b-MV injection while the protein content of its target gene PPAR-γ was significantly suppressed, together with a significant up-regulation of the lipolysis genes, hormone sensitive lipase, monoglyceride lipase and leptin. Moreover, miR-130b-MV injection increased the expression of miR-378a and miR-378-3p that are reported to participate in the regulation of fat deposition. Conclusion: Our results indicate that miR-130b-MV is able to reduce the epididymal fat deposition and partly restore glucose tolerance, through translational repression of PPAR-γ in a high-fat diet-induced obese mouse model.
    Full-text · Article · Oct 2015
    • "For example, weight control is determined by neural, endocrine, intestinal and psychological aspects beyond adiposity [7]. Obesity is characterized by a low-grade chronic inflammation of the adipose tissue, since fat plays the role of a secretory organ for signaling molecules; therefore obesity is considered an inflammatory process, increasing the circulation of pro-inflammatory cytokines [5]; mainly pro-inflammatory adipokines such as TNF-α, IL-6, decreasing the levels of anti-inflammatory adipokines as Interleukin 10 (IL-10) [1,2,6,7]. Adipokine is a general term adopted to describe the proteins secreted (and synthesized) by fat tissue, this protein being a cytokine or not. "
    Full-text · Article · Sep 2015
    • "Thus, strategies and policies for prevention and treatment of obesity have been deemed global priorities to reverse the trend of the global obesity epidemic [1]. Numerous anti-obesity interventions have been studied including lifestyle modification, behavioral therapy, pharmacological treatments, and surgery [6,7]. However, the limited efficacy and high incidence of adverse events with side effects observed in conventional therapies have motivated practitioners to investigate complementary and alternative medicine therapies for weight loss such as dietary supplements, herbal products, and acupuncture [8,9] . "
    [Show abstract] [Hide abstract] ABSTRACT: To examine the effect and safety of high-dose green tea extract (Epigallocatechin gallate, EGCG) at a daily dosage of 856.8 mg on weight reduction and changes of lipid profile and obesity-related hormone peptides in women with central obesity. We conducted a randomized, double-blind trial registered under ClinicalTrials.gov Identifier no. NCT02147041. A total of 115 women with central obesity were screened at our clinic. 102 of them with a body mass index (BMI) ≥ 27 kg/m(2) and a waist circumference (WC) ≥ 80 cm were eligible for the study. These women were randomly assigned to either a high-dose green tea group or placebo group. The total treatment time was 12 weeks. The main outcome measures were anthropometric measurements, lipid profiles, and obesity related hormone peptides including leptin, adiponectin, ghrelin, and insulin. Significant weight loss, from 76.8 ± 11.3 kg to 75.7 ± 11.5 kg (p = 0.025), as well as decreases in BMI (p = 0.018) and waist circumference (p = 0.023) were observed in the treatment group after 12 weeks of high-dose EGCG treatment. This study also demonstrated a consistent trend of decreased total cholesterol, reaching 5.33%, and decreased LDL plasma levels. There was good tolerance of the treatment among subjects without any side effects or adverse events. Significantly lower ghrelin levels and elevated adiponectin levels were detected in the study group than in the placebo group. 12 weeks of treatment with high-dose green tea extract resulted in significant weight loss, reduced waist circumference, and a consistent decrease in total cholesterol and LDL plasma levels without any side effects or adverse effects in women with central obesity. The antiobestic mechanism of high-dose green tea extract might be associated in part with ghrelin secretion inhibition, leading to increased adiponectin levels. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Full-text · Article · May 2015
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