International journal of obesity supplements最新文献

Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis. A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology. Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondrial hydrogen peroxide (H₂O₂) emission and a shift to a more oxidized intracellular redox environment. Blocking H₂O₂ emission prevents the shift in redox environment and preserves insulin sensitivity, providing evidence that the mitochondrial respiratory system is able to sense and respond to cellular metabolic imbalance. Mitochondrial H₂O₂ emission is a major regulator of protein redox state, as well as the overall cellular redox environment, raising the intriguing possibility that elevated H₂O₂ emission from nutrient overload may represent the underlying basis for the development of insulin resistance due to disruption of normal redox control mechanisms regulating protein function, including the insulin signaling and glucose transport processes.

Consumption of a high-fat diet has been linked to obesity, dyslipidemia and cardiovascular disease. Less well appreciated are adverse effects on the brain and behavior. Recent research has shown that consumption of a high-fat diet can alter gene expression within the brain, and the dopamine and opioid neurotransmitter systems appear to be vulnerable to dysregulation. This review will focus on recent reports in both humans and animal models that describe adverse effects of high-fat diet consumption on the central reward circuitry. In addition, the importance of different development windows will be discussed, with effects observed in both the prenatal/perinatal time period and with chronic high-fat diet consumption in adulthood.

Overfeeding high-fat (HF) meals results in both short-term and long-term effects that vary depending upon adiposity status (obese vs nonobese) and family history of type 2 diabetes. Although more than 4 weeks of overeating produces mild insulin resistance, whether the same is true of a single, HF meal is not clear. We reviewed overfeeding studies of 4-8 weeks duration, studies of single HF meals and our own (unpublished) plasma insulin and glucose concentration data from 59 nonobese and 15 overweight/obese volunteers who consumed either a normal-fat (NF) breakfast or a breakfast matched for carbohydrate and protein, but with an additional 80 g of monounsaturated fat (HF). Four to eight weeks of overfeeding a HF diet causes an ∼10% reduction in insulin sensitivity. Some authors report that a single HF meal is associated with greater postprandial insulin concentrations, whereas other investigators have not confirmed such a response. We found that plasma glucose concentrations peaked later following a HF breakfast than a NF breakfast in both obese and nonobese adults and that daytime plasma insulin concentrations were not uniformly increased following a HF breakfast. We conclude that a single HF meal delays the postprandial peak in glucose concentrations, likely due to delayed gastric emptying. This will confound attempts to use insulinemia as a marker of insulin resistance. After 4-8 weeks of overeating a HF diet accompanied by 2-4 kg of fat gain, insulin sensitivity decreases by ∼10%. Although we could not demonstrate that baseline insulin resistance predicts visceral fat gain with overfeeding, normal-weight relatives of type 2 diabetes mellitus do tend to gain more weight and become more insulin resistant than those without a positive family history of type 2 diabetes mellitus. In summary, short-term weight gain from HF diets induces relatively mild metabolic disorders.

The significant increase in childhood obesity has become a particular concern, and it is recognized that the programming of obesity can arise from events occurring in the peri-conception period, prenatally and/or during the early postnatal period. In particular, high intake of dietary fat by the mother has long-term effects that are worse than once thought. This symposium was designed to outline some of the important consequences of maternal high-fat feeding during gestation and lactation, as well as exposure to a high-fat diet (HFD) after weaning, on the programming of homeostatic and hedonic regulation of food intake in both rodents and nonhuman primates (NHPs). Although a consensus emerges that high-fat feeding in early development increases the risk of developing obesity and the metabolic syndrome in adulthood, there is less agreement on the mechanisms through which this risk is conferred. Epigenetic modifications in specific gene promoters within the dopaminergic reward pathways and on the histone code will be discussed. We will also examine the effects of metabolic hormones such as leptin and ghrelin to shape the early development of hypothalamic projections that are critical to control food intake; finally, the importance of placental function in increasing obesity risk in NHP fetus from HFD mothers will be debated.

The observation that events occurring after consumption of a meal can directly affect metabolic risk has been gaining interest over the past 40 years. As a result, the desire for investigators to conduct postprandial studies has also increased. Study design decisions pertaining to the choice of meal quantity and composition are more difficult than may be readily apparent, and there is now ample evidence available in the literature to suggest that what is fed on the test day significantly affects postprandial metabolism and can therefore influence interpretation of results. In addition, events occurring before the testing day (food intake and activities) can also have an impact on the observed postprandial response. The goal of this review is to present aspects of study design critical to the investigation of postprandial metabolism. These details include subject preparation, meal quantity, form and composition, as well as sampling protocols for measuring metabolites. Key factors and practical examples are provided to minimize the impact of nonresearch variables on subject variability. Finally, aspects related to using stable isotope tracers to measure metabolism of meal fat are discussed, including choice of tracer form, dose and delivery in food. Given that fed-state events contribute significantly to chronic disease risk, improved methods to study the absorption and disposal of food energy will support the development of strategies designed to prevent and treat diseases associated with overconsumption of nutrients.

In light of the limited long-term success of obesity treatments, it is tempting to consider the elusive goal of 'treatment matching', in which characteristics of individuals are optimally matched to targeted treatments to improve success. Previous frameworks for treatment matching in obesity have primarily focused on basic physiological characteristics, such as initial degree of overweight, and on treatment intensity, such as stepped-care alternatives (self-help manuals, group support, medication and surgery). Few studies have empirically evaluated the success of these frameworks. Given recent advances in genomics, neuroscience and other fields, both the breadth of domains and combinations of individuals' characteristics that could be used for treatment matching have increased markedly. Although the obesity field seems poised to build on these advances, a crucial challenge remains regarding the treatments themselves. Ultimately, the success of treatment matching will rely on identifying treatment intervention components with well-differentiated and empirically supported mediators, that is, clear insights into how intervention components work. Here we examine the scope of this challenge specifically for the design of efficacious psychosocial and behavioral intervention components, and identify areas for future research.

Although the 'Low-Fat' diet was the predominant public health recommendation for weight loss and weight control for the past several decades, the obesity epidemic continued to grow during this time period. An alternative 'low-carbohydrate' (Low-Carb) approach, although originally dismissed and even vilified, was comparatively tested in a series of studies over the past decade, and has been found in general to be as effective, if not more, as the Low-Fat approach for weight loss and for several related metabolic health measures. From a glass half full perspective, this suggests that there is more than one choice for a dietary approach to lose weight, and that Low-Fat and Low-Carb diets may be equally effective. From a glass half empty perspective, the average amount of weight lost on either of these two dietary approaches under the conditions studied, particularly when followed beyond 1 year, has been modest at best and negligible at worst, suggesting that the two approaches may be equally ineffective. One could resign themselves at this point to focusing on calories and energy intake restriction, regardless of macronutrient distributions. However, before throwing out the half-glass of water, it is worthwhile to consider that focusing on average results may mask important subgroup successes and failures. In all weight-loss studies, without exception, the range of individual differences in weight change within any particular diet groups is orders of magnitude greater than the average group differences between diet groups. Several studies have now reported that adults with greater insulin resistance are more successful with weight loss on a lower-carbohydrate diet compared with a lower-fat diet, whereas adults with greater insulin sensitivity are equally or more successful with weight loss on a lower-fat diet compared with a lower-carbohydrate diet. Other preliminary findings suggest that there may be some promise with matching individuals with certain genotypes to one type of diet over another for increasing weight-loss success. Future research to address the macronutrient intake component of the obesity epidemic should build on these recent insights and be directed toward effectively classifying individuals who can be differentially matched to alternate types of weight-loss diets that maximize weight-loss and weight-control success.

Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance. T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation. Recently, we made the surprising discovery that B cells are important contributors to this process. Thus, some B cells and the antibodies they produce can promote VAT-associated and systemic inflammation, leading to insulin resistance. This report will focus on the properties of these B cells, and how they contribute to insulin resistance through T-cell modulation and production of pathogenic autoantibodies. Understanding the mechanisms by which B cells contribute to insulin resistance should lead to new antibody-based diagnostics and B-cell modulating therapeutics to manage this increasingly prevalent disease.

Childhood obesity represents a worldwide medical and public health challenge. Academic medical centers cannot avoid the effects of the obesity epidemic, and must adopt strategies for their academic, clinical and public policy responses to childhood obesity. The Center for Healthy Weight at Stanford University and Lucile Packard Children's Hospital at Stanford provides an example and model of one such strategy. The design provides both breadth and depth through six cores: Research, Patient Care, Community Programs, Advocating for Public Policy Change, Training and Professional Education, and the Healthy Hospital Initiative. The Center and its cores are designed to facilitate interdisciplinary collaboration across the university, medical school, children's hospital and surrounding community. The foci of these cores are likely to be relevant to almost any academic medical center's mission and functions.

Over two-thirds of the United States is overweight or obese, and over 5% of the country is morbidly obese. Numerous public health preventative measures have been established to help battle this public health epidemic. Surgical obesity treatment, although now gaining popularity, has been an underutilized treatment option for obesity. Patients with a body mass index (BMI) of >40 or >35 kg m^-2 with two or more comorbid conditions are eligible for bariatric surgery. Currently, the three most popular bariatric surgeries are Roux-en-y gastric bypass, sleeve gastrectomy and gastric banding procedures, all overwhelmingly performed laparoscopically. The purpose of this article is to discuss the heterogeneity of bariatric surgery. In our practice, among 834 patients operated over a 4-year period (2006-2010), patients were of an average age of 45 years (16-73 years), 80.4% were female patients, 82.5% had private insurance, 61% were White, 17% were Hispanic and 9% were Black. Patients had an average BMI of 46.2 kg m^-2 (30.1-75.3 kg m^-2), waist circumference of 133.6 cm (68.6-207.8 cm) and four preoperative comorbidities (0-11 comorbidities). Variation exists in surgeon practice patterns for preoperative weight-loss recommendations and complication rates based on surgery case volume. Despite variation in patient, surgeon and hospital characteristics, bariatric surgery outcomes are generally highly safe and effective.