Body composition, IGF1 status, and physical functionality in nonagenarians: implications for osteosarcopenia

OBJECTIVES: Body composition alterations occur during aging. The purpose of the present analysis was to explore the functional consequences of the overlap of sarcopenia and osteoporosis, and the potential role of insulin-like growth factor 1 (IGF1) in their development in the oldest old. SETTING AND PARTICIPANTS: Eighty-seven nonagenarians from the Louisiana Healthy Aging Study were included. MEASURES: The definition of sarcopenia was based on appendicular lean mass (ALM). Osteoporosis was diagnosed based on bone mineral density (BMD) T score. Four phenotypes were compared: (1) healthy body composition, that is, nonosteoporotic nonsarcopenic (CO, control group), (2) osteoporotic (O, low BMD T score), (3) sarcopenic (S, low ALM), and (4) osteosarcopenic (OS, low BMD T score and low ALM). Sex- and age-specific IGF1-Standard Deviation Scores (SDS) were calculated. The Continuous Scale-Physical Functional Performance (CS-PFP) test was performed. RESULTS: In OS men, IGF1-SDS values (-0.61 ±0.37 vs -0.04 ± 0.52, P = .02) were lower than those in CO males (control group), whereas IGF1-SDS were similar in the 4 body composition phenotypes in women. In men only, ALM was positively associated with IGF1-SDS values (P = .01) independent of age and C-reactive protein concentration. Regarding bone health, we found no association between IGF1-SDS values and BMD. IGF1-SDS was not associated with functional performance (CS-PFP) in men and women. CONCLUSIONS/IMPLICATIONS: IGF1 sensitivity in skeletal muscle and bone may differ by sex in the oldest old. IGF1 status did not appear to affect physical functionality. Determinants and clinical and functional characteristics of osteosarcopenia need to be further investigated in order to define conclusive diagnostic criteria

Carbohydrate utilization in obese subjects after an oral load of 100 g naturally-labelled [13C] glucose

1. Total carbohydrate (CHO) and ingested glucose oxidation was measured in five obese subjects with normal glucose tolerance after an oral load of 100g naturally-labelled [13C]glucose using indirect calorimetry and mass spectrometry respectively. 2. CHO utilization rate (107 ± 14 mg/min in the post-absorptive state) increased 30 min after the glucose load to reach a plateau (245±25 mg/min) between 90 and 120 min. It then decreased to basal values at 330 min. Cumulative CHO oxidation over 480 min was 66±7 g and the CHO oxidized above basal levels was 26 ± 7g. 3. Enrichment of expired carbon dioxide with 13c began at 45 min and maximum values were observed between 210 and 300 min. At 480 min, cumulative oxidation of the ingested glucose was 24± 2 g. 4. Compared with controls, the obese subjects exhibit an impairment of CHO utilization which precedes glucose intolerance. This impairment can be explained by an increased availability of free fatty acids which favours lipid oxidation at the expense of ingested [13C]glucose oxidatio

Activity related energy expenditure, appetite and energy intake. Potential implications for weight management

The aim was to investigate relationships between activity related energy expenditure (AREE), appetite ratings and energy intake (EI) in a sample of 40 male (26.4years; BMI 23.5kg/m2) and 42 female (26.9years; BMI 22.4kg/m2) participants. AREE was expressed as the residual value of the regression between total daily EE (by doubly labeled water) and resting EE (by indirect calorimetry). EI was measured using an ad libitum buffet meal and visual analogue scales measured subjective appetite ratings before and after the meal. AREE was divided into low, middle and high sex-specific tertiles. General linear models were used to investigate differences in appetite ratings and EI across AREE tertiles. Before the meal, males in the high AREE tertile had significantly lower desire to eat and lower prospective food consumption and higher feelings of fullness compared to those in the low tertile. Males in the middle tertile had significantly higher satiety quotients after the meal and lower EI compared to the other tertiles. No significant differences across tertiles were found in females. Sex differences in relationships between AREE, appetite ratings and EI may lead to differing patterns of EI and subsequent weight maintenance

Caveolin-1 expression and cavin stability regulate caveolae dynamics in adipocyte lipid store fluctuation

Adipocytes specialized in the storage of energy as fat are among the most caveolae-enriched cell types. Loss of caveolae produces lipodystrophic diabetes in humans, which cannot be reversed by endothelial rescue of caveolin expression in mice, indicating major importance of adipocyte caveolae. However, how caveolae participate in fat cell functions is poorly understood. We investigated dynamic conditions of lipid store fluctuations and demonstrate reciprocal regulation of caveolae density and fat cell lipid droplet storage. We identified caveolin-1 expression as a crucial step in adipose cell lines and in mice to raise the density of caveolae, to increase adipocyte ability to accommodate larger lipid droplets, and to promote cell expansion by increased glucose utilization. In human subjects enrolled in a trial of 8 weeks of overfeeding to promote fattening, adipocyte expansion response correlated with initial caveolin-1 expression. Conversely, lipid mobilization in cultured adipocytes to induce lipid droplet shrinkage led to biphasic response of cavin-1 with ultimate loss of expression of cavin-1 and -3 and EHD2 by protein degradation, coincident with caveolae disassembly. We have identified the key steps in cavin/caveolin interplay regulating adipocyte caveolae dynamics. Our data establish that caveolae participate in a unique cell response connected to lipid store fluctuation, suggesting lipid-induced mechanotension in adipocytes

Safety of two-year caloric restriction in non-obese healthy individuals

BACKGROUND: The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated. OBJECTIVE: Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults. DESIGN: A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored. RESULTS: Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal-weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group. CONCLUSIONS: Two-years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important

Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects.

Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. [email protected] OBJECTIVE: The new uncoupling proteins, UCP2 and UCP3, are thought to play a role in energy efficiency in humans. Endurance training has been suggested to have effects on resting metabolic rate and energy efficiency. We therefore determined UCP2 and UCP3 mRNA levels in skeletal muscle of trained and untrained male subjects. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), expression of UCP2, UCP3L and UCP3S mRNA were measured in muscle biopsies from the quadriceps femoris in eight trained (23.9+/-1.6 y; 70.6+/-3.1 kg; 14+/-3% body fat; maximal power output (Wmax): 5. 6+/-0.4 W/kg; mean+/-s.d.) and 10 lean, untrained (22.1+/-2.9 y; 72. 0+/-7.9 kg; 18+/-4% body fat; Wmax: 3.9+/-0.4 W/kg; mean+/-s.d.) subjects. In six of the trained subjects, UCP2 and UCP3 mRNA were measured before and after an exercise bout to exhaustion. To correct for differences in mitochondrial content, levels of UCP2 and UCP3 mRNA were expressed relative to cytochrome-b, a marker of mitochondrial content. RESULTS: Acute exercise had no effect on the expression of UCP3L or UCP3S, but in five out of six subjects UCP2 expression decreased after exercise, although the difference was not statistically significant (P=0.11). Trained subjects had significantly reduced mRNA levels of UCP3L (P=0.028) and UCP3S (P=0. 031). VO2max expressed per kg of fat-free mass was negatively correlated with UCP3L (r=-0.61, P=0.009) and UCP3S (r=-0.52, P=0. 028). Mechanical efficiency correlated negatively with UCP3L (r=-0. 56, P=0.019), UCP3S (r=-0.47, P=0.048) and tended to correlate with UCP2 (r=-0.46, P=0.06). CONCLUSION: The lower levels of UCP3 mRNA in trained subjects and the inverse relationship of UCP3 expression and mechanical efficiency suggest that exercise training produces an adaptive physiological response in skeletal muscle improving mechanical efficiency