THE PENNINGTON CALERIE TEAMOBJECTIVE -The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (S i ) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS-Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction ϩ12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and S i were assessed at baseline and month 6. RESULTS -At baseline, FCS was related to VAT and IHL (P Ͻ 0.05) but not to IMCL. FCS was also the strongest determinant of S i (P Ͻ 0.01). Weight loss at month 6 was 1 Ϯ 1% (control, mean Ϯ SE), 10 Ϯ 1% (CR), 10 Ϯ 1% (CREX), and 14 Ϯ 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P Ͻ 0.01), but IMCL was unchanged. S i was increased at month 6 (P ϭ 0.05) in the CREX (37 Ϯ 18%) and LCD (70 Ϯ 34%) groups (P Ͻ 0.05) and tended to increase in the CR group (40 Ϯ 20%, P ϭ 0.08). Together the improvements in S i were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS.CONCLUSIONS -Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

AimsPeak oxygen uptake (VO 2 ) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients. Methods and resultsEleven HFpEF patients (73 + 7 years, 7 females/4 males) and 13 healthy controls (70 + 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q c , acetylene rebreathing) response to exercise was determined from linear regression of Q c and VO 2 (Douglas bags) at rest, 30% and 60% of peak VO 2 , and maximal exercise. Peak VO 2 was lower in HFpEF patients than in controls (13.7 + 3.4 vs. 21.6 + 3.6 mL/kg/min; P , 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output ConclusionContrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO 2 , increased DQ c /DVO 2 slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.--

Magnetic resonance spectroscopy studies have shown that intramyocellular lipids (IMCL) and liver fat (LFAT) levels vary with insulin sensitivity and obesity, which are common in the elderly. Thus, magnetic resonance spectroscopy was used to investigate the hypothesis that IMCL and LFAT are increased in the elderly. IMCL and LFAT in young (aged 20-32 yr) and elderly (aged 65-74 yr) were measured fasted, and glucose, insulin, total free fatty acids levels, and free fatty acids profiles were measured during a 2-h oral glucose tolerance test. Body fat percentage was determined with dual x-ray absorptiometry. The elderly had significantly greater IMCL (0.12 +/- 0.01 vs. 0.08 +/- 0.01, mean +/- sem; P = 0.01) and LFAT (0.28 +/- 0.06 vs. 0.08 +/- 0.01; P = 0.004; expressed as ratios to Intralipid standard) than the young. The elderly had increased insulin resistance as calculated by the Matsuda model compared with the young (5.1 +/- 0.9 vs. 9.9 +/- 1.4; P = 0.02). Regression analysis of all subjects indicated that the increases in IMCL and LFAT were correlated with insulin sensitivity, glycosylated hemoglobin, plasma lipids, and body fat. Furthermore, the correlation between insulin sensitivity and IMCL and LFAT remained significant, after accounting for the effect of body fat. Increases of IMCL and LFAT occur in elderly individuals and may be related to insulin resistance.

The MRI-determined muscle size indices, which were specific to the triceps surae, correlated with strength better than whole limb anthropometric and DEXA indices. In this group of women, both ACSA and PCSA appeared superior to VOLm for predicting strength. PCSA was not found to be more precise than ACSA. ACSA appears to provide adequate precision for estimating plantar flexor specific tension in vivo.

objective: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures: Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m 2 ) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results: At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion: CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.