Mark B. Cope

Obesity Among Those with Mental Disorders: A National Institute of Mental Health Meeting Report

The National Institute of Mental Health convened a meeting in October 2005 to review the literature on obesity, nutrition, and physical activity among those with mental disorders. The findings of this meeting and subsequent update of the literature review are summarized here. Levels of obesity are higher in those with schizophrenia and depression, as is mortality from obesity-related conditions such as coronary heart disease. Medication side effects, particularly the metabolic side effects of antipsychotic medications, contribute to the high levels of obesity in those with schizophrenia, but increased obesity and visceral adiposity have been found in some but not all samples of drug-naïve patients as well. Many of the weight-management strategies used in the general population may be applicable to those with mental disorders, but little is known about the effects of these strategies on this patient population or how these strategies may need to be adapted for the unique needs of those with mental disorders. The minimal research on weight-management programs for those with mental disorders indicates that meaningful changes in dietary intake and physical activity are possible. Physical activity is an important component of any weight-management program, particularly for those with depression, for which a substantial body of research indicates both mental and physical health benefits. Obesity among those with mental disorders has not received adequate research attention, and empirically-based interventions to address the increasing prevalence of obesity and risk of cardiovascular and metabolic diseases in this population are lacking.

White hat bias: examples of its presence in obesity research and a call for renewed commitment to faithfulness in research reporting

‘White hat bias’ (WHB) (bias leading to distortion of information in the service of what may be perceived to be righteous ends) is documented through quantitative data and anecdotal evidence from the research record regarding the postulated predisposing and protective effects of nutritively sweetened beverages and breastfeeding, respectively, on obesity. Evidence of an apparent WHB is found in a degree sufficient to mislead readers. WHB bias may be conjectured to be fuelled by feelings of righteous zeal, indignation toward certain aspects of industry or other factors. Readers should beware of WHB, and our field should seek methods to minimize it.

Critical review of the World Health Organization's (WHO) 2007 report on 'evidence of the long-term effects of breastfeeding: systematic reviews and meta-analysis' with respect to obesity.

Obesity among children and adults has become a highly recognized public health concern and there is an increasing need to discover causes and evaluate preventative measures. One putatively causal influence on obesity is breastfeeding (BF). The World Health Organization (WHO) recently published a report (WR) on ‘Evidence of the Long‐Term Effects of Breastfeeding: Systematic Reviews and Meta‐Analysis’ and concluded ‘that the evidence suggests that breastfeeding may have a small protective effect[emphasis added] on the prevalence of obesity . . . [and] the effect of breastfeeding was not likely to be due to publication bias or confounding.’ Here we provide a critical overview of the WRs section on BF and obesity by addressing eight questions: Q1: Is there sufficient evidence to conclude that BF is associated with lower rates of obesity in children? Q2: Is there sufficient evidence to conclude that BF is associated with lower rates of obesity among breastfed offspring once they reach adulthood? Q3: If there are such associations, what are their magnitudes in comparison with other putatively causal factors and with respect to the potential impact on individual or population levels of obesity? Q4: Is there sufficient evidence to conclude that BF causes a reduction in risk of obesity during childhood? Q5: Is there sufficient evidence to conclude that BF does not cause a reduction in risk of obesity during childhood? Q6: Is there sufficient evidence to conclude that BF causes a long‐term reduction in risk of obesity that persists into adulthood? Q7: Is there sufficient evidence to conclude that BF does not cause a long‐term reduction in risk of obesity that persists into adulthood? Q8: What further research might be done to address these questions? We conclude that, while BF may have benefits beyond any putative protection against obesity, and benefits of BF most likely outweigh any harms, any statement that a strong, clear or consistent body of evidence shows that BF causally reduces the risk of overweight or obesity is unwarranted at this time.

Antipsychotic drug-induced weight gain: development of an animal model

OBJECTIVE:Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition.METHODS:Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment.RESULTS:After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased.CONCLUSIONS:Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

Protein blend ingestion following resistance exercise promotes human muscle protein synthesis.

High-quality proteins such as soy, whey, and casein are all capable of promoting muscle protein synthesis postexercise by activating the mammalian target of rapamycin (mTORC1) signaling pathway. We hypothesized that a protein blend of soy and dairy proteins would capitalize on the unique properties of each individual protein and allow for optimal delivery of amino acids to prolong the fractional synthetic rate (FSR) following resistance exercise (RE). In this double-blind, randomized, clinical trial, 19 young adults were studied before and after ingestion of ∼19 g of protein blend (PB) or ∼18 g whey protein (WP) consumed 1 h after high-intensity leg RE. We examined mixed-muscle protein FSR by stable isotopic methods and mTORC1 signaling with western blotting. Muscle biopsies from the vastus lateralis were collected at rest (before RE) and at 3 postexercise time points during an early (0-2 h) and late (2-4 h) postingestion period. WP ingestion resulted in higher and earlier amplitude of blood branched-chain amino acid (BCAA) concentrations. PB ingestion created a lower initial rise in blood BCAA but sustained elevated levels of blood amino acids later into recovery (P < 0.05). Postexercise FSR increased equivalently in both groups during the early period (WP, 0.078 ± 0.009%; PB, 0.088 ± 0.007%); however, FSR remained elevated only in the PB group during the late period (WP, 0.074 ± 0.010%; PB, 0.087 ± 0.003%) (P < 0.05). mTORC1 signaling similarly increased between groups, except for no increase in S6K1 phosphorylation in the WP group at 5 h postexercise (P < 0.05). We conclude that a soy-dairy PB ingested following exercise is capable of prolonging blood aminoacidemia, mTORC1 signaling, and protein synthesis in human skeletal muscle and is an effective postexercise nutritional supplement.

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.

Soy-Dairy Protein Blend and Whey Protein Ingestion After Resistance Exercise Increases Amino Acid Transport and Transporter Expression in Human Skeletal Muscle

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein.

The potential role of soyfoods in weight and adiposity reduction: an evidence-based review

Evidence concerning the relationship between soyfoods and weight loss was reviewed. Detailed searches of PubMed and Web of Science were performed to identify and evaluate evidence for or against four propositions related to soyfoods and weight loss (Data from in vitro, animal, epidemiologic, and clinical studies were evaluated and summarized). (1) Certain soyfoods will improve weight and/or fat loss when fed at isolcaloric levels (similar calories given across experimental conditions, but not necessarily at a level to maintain current body weight); generally supportive evidence in animal studies, but there is no compelling support in human studies. (2) Certain soyfoods will improve weight and fat loss when included as part of a diet by affecting caloric intake; limited supportive evidence in animal and human studies. (3) Certain soyfoods will prevent/improve risk factors related to glucoregulatory function and cardiovascular health during weight loss; some evidence supporting this proposition, but additional evidence is needed before conclusions can be made. (4) Certain soyfoods will minimize the loss of bone mass during weight loss; no data available pertinent to this proposition. Limitations in existing data make it difficult to reach conclusions regarding these four propositions. Overall, the current data suggest that soyfoods are as good as other protein sources for promoting weight loss and there is a suggestive body of evidence that soyfoods may confer additional benefits, but results must be carefully interpreted and additional evidence is needed before making firm conclusions concerning soyfoods and weight loss.

Risperidone alters food intake, core body temperature, and locomotor activity in mice.

Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p=0.050) and gained more weight (p=0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p=0.046), but not body temperature (p=0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p=0.0001), and tended to be higher during the dark phase (p=0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p=0.006); there were no differences in activity during the light phase (p=0.47). UCP1 (p<0.01) and UCP3 (p<0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p<0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.

Obesity: person and population.

COPE, MARK B. AND DAVID B. ALLISON. Obesity: person and population.