Howard Eisenson

A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.

Sleep disturbance and pain in an obese residential treatment-seeking population

BackgroundThe relationships between body mass index (BMI) and sleep disturbance, sleep disturbance and pain, and obesity and pain are documented; however, there is a paucity of research exploring how sleep relates to pain in obese populations. MethodThe participants comprized 386 (234 women, 152 men) obese (BMI M=40.7) adult (age M=51.0 y) patients enrolling in a 4-week residential obesity treatment program. All information was gathered as part of the initial program evaluation. ResultsThe prevalence of patients reporting at least 1 disturbed sleep symptom was 84.8%. The prevalence of patients reporting at least 1 type of pain was 83.4%. After controlling for depression, anxiety, BMI, age, and sleep apnea treatment, regression analyses showed that daytime sleepiness, night sweats (P<0.01), difficulties falling asleep, and difficulties staying asleep (P<0.05) predicted the total number of pain symptoms reported by women. Among men, controlling for the same variables, fatigue (P<0.01), night sweats, and difficulty falling asleep (P<0.05) predicted the number of pain symptoms reported. DiscussionThese results suggest that in this obese population, disturbed sleep and pain are related, and that this relationship may be different in men and women. Given the prevalence of pain and disturbed sleep in obese populations, this represents a valuable first step in better understanding this relationship.

Serum aminotransferase changes with significant weight loss: sex and age effects

In obese subjects, the liver may be differentially affected by significant weight loss depending on as yet unknown factors. We explored clinical factors associated with serum alanine aminotransferase (ALT) changes during significant weight loss in a residential weight loss program. Clinical data from 362 adults who received a comprehensive weight loss intervention (ie, diets, physical fitness, and behavioral modification) in the program were analyzed. Serum ALT was used as a surrogate marker of liver injury. The ALT changes during the program were calculated to create study outcome categories (improvement, no change, or deterioration of ALT during significant weight loss). Variables of demography, lifestyle, and comorbidities at baseline, and total/rate of weight change during the program were explored for associations with the ALT change categories using multiple logistic regression models. Variation by sex was apparent among predictors of ALT deterioration; men with rapid weight loss and women with higher initial body mass index were more likely to experience ALT deterioration, whereas men with prior alcohol consumption were less likely to experience ALT deterioration even after adjusting for baseline ALT (Ps < .03). Variation by age was apparent among predictors of ALT improvement; younger patients with current smoking and older patients with rapid weight loss, diabetes or impaired fasting glucose, or sleep apnea or who followed a reduced-carbohydrate diet were less likely to experience ALT improvement (Ps < .05). A number of clinical factors influence ALT changes during weight loss in sex- and age-specific manners. The patterns that we detected may have pathophysiologic significance beyond the practical implications of our findings in clinical practice related to underlying changes in fat metabolism.

Improvements in Functional Exercise Capacity after a Residential Behavioural Change, Diet and Fitness Program for Obese Adults

BACKGROUND AND PURPOSE Obese adults are at an increased risk for mobility-related problems. National guidelines recommend calorie restrictions and exercise for obese adults as a means to improve functional fitness capacity and to increase mobility. Yet, lifestyle weight loss interventions often fail to measure fitness changes. The aim of this study was to assess whether a 1-month, intensive behavioural change, diet and fitness intervention for overweight and obese adults would result in statistically significant and clinically meaningful changes in functional exercise. METHODS A pre-post test design was used in this study. Seventy-two participants (40 women, 32 men; mean baseline body mass index (BMI) = 42.6 + 9.0; mean age = 45.8 + 16.8) completed a modified 6-minute walk test (6MWT), performed on a treadmill, at baseline and at end of treatment. RESULTS Significant improvements included decreased BMI (2.7 + 1.7 kg m(-2) , p < 0.001) and increased 6MWT distance (66.4 + 73.0 m, p < 0.001). The 6MWT improved by 66 m on average, a reported clinically meaningful difference. Greater improvements in the 6MWT were significantly correlated with greater weight loss and BMI reduction. DISCUSSION Our findings suggest that rehabilitation beyond weight loss may be derived from participation in a brief, intensive behavioural change, diet and fitness programme. Physiotherapists are in a prime position to address the physical and motivational challenges participants face while living with severe obesity: targeting functional exercise capacity is one key strategy for addressing immobility associated with obesity. Copyright