Daniel L. Smith

Myths, Presumptions, and Facts about Obesity

BACKGROUND Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information. METHODS Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations. RESULTS We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations. CONCLUSIONS False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.).

Identification of Brown Adipose Tissue in Mice with Fat-Water IDEAL-MRI

To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat–water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).

Metformin Supplementation and Life Span in Fischer-344 Rats

Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.

MR properties of brown and white adipose tissues

To explore the MR signatures of brown adipose tissue (BAT) compared with white adipose tissue (WAT) using single‐voxel MR spectroscopy.

Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

Calorie restriction: what recent results suggest for the future of ageing research

Eur J Clin Invest 2010; 40 (5): 440–450

Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice.

To investigate the variations in body weight, food intake, and body composition of both male and female C57BL/6J mice during a diet‐induced obesity model with high‐fat diet (HFD) feeding.

Mild Calorie Restriction Induces Fat Accumulation in Female C57BL/6J Mice

This study investigated the effects of mild calorie restriction (CR) (5%) on body weight, body composition, energy expenditure, feeding behavior, and locomotor activity in female C57BL/6J mice. Mice were subjected to a 5% reduction of food intake relative to baseline intake of ad libitum (AL) mice for 3 or 4 weeks. In experiment 1, body weight was monitored weekly and body composition (fat and lean mass) was determined at weeks 0, 2, and 4 by dual energy X‐ray absorptiometry. In experiment 2, body weight was measured every 3 days and body composition was determined by quantitative magnetic resonance weekly, and energy expenditure, feeding behavior, and locomotor activity were determined over 3 weeks in a metabolic chamber. At the end of both experiments, CR mice had greater fat mass (P < 0.01) and less lean mass (P < 0.01) compared with AL mice. Total energy expenditure (P < 0.05) and resting energy expenditure (P < 0.05) were significantly decreased in CR mice compared with AL mice over 3 weeks. CR mice ate significantly more food than AL mice immediately following daily food provisioning at 1600 hours (P < 0.01). These findings showed that mild CR caused increased fat mass, decreased lean mass and energy expenditure, and altered feeding behavior in female C57BL/6J mice. Locomotor activity or brown adipose tissue (BAT) thermogenic capacity did not appear to contribute to the decrease in energy expenditure. The increase in fat mass and decrease in lean mass may be a stress response to the uncertainty of food availability.

Impact of weight cycling on risk of morbidity and mortality.

Unintentional weight gain is commonly observed in adult humans, often provoking intentional weight loss attempts followed by unintentional weight regain. This episodic variation in body weight over a period of time has been referred to as ‘weight cycling’. Over the last two decades, weight cycling has been associated with a number of morbid health conditions and increased mortality. This article provides a comprehensive evaluation of recent weight‐cycling evidence, looks to understand design differences between studies and study outcomes, assesses the need for further research on particular health outcomes, and proposes alternative methodologies that will bridge the needs and capabilities of research. Searches were conducted per PRISMA guidelines. Articles on weight cycling in the literature were initially identified using search strings in PubMed. Eligibility assessment of the remaining articles was performed independently by three reviewers to identify publications that presented direct evidence. Twenty human studies (in addition to seven animal studies) were selected and retained; 12 accounted for the intentionality of weight loss. Although weight regain following successful weight loss remains one of the most challenging aspects of body‐weight regulation, evidence for an adverse effect of weight cycling appears sparse, if it exists at all.

Variations in T2* and Fat Content of Murine Brown and White Adipose Tissues by Chemical-Shift MRI

PURPOSE The purpose was to compare T(2)* relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. MATERIALS AND METHODS A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T(2)*-corrected chemical-shift-based water-fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T(2)* and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T(2)* and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test. RESULTS Significant differences (P<.01) in BAT T(2)* and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T(2)* and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T(2)* and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images. CONCLUSION T(2)* and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the formers greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter.