Differences in muscle energy metabolism and metabolic flexibility between sarcopenic and nonsarcopenic older adults

Abstract

Background: Metabolic flexibility is the ability of skeletal muscle to adapt fuel utilization to the demand for fuel sources [carbohydrates (CHO) and fats (FAT)]. The purpose of this study was to explore muscle energy metabolism and metabolic flexibility under various conditions in sarcopenic (S) versus nonsarcopenic (NS) older adults.

Methods: Twenty-two older adults aged 65 years or older were categorized as NS [n = 11; mean ± standard deviation (SD); age = 73.5 ± 6.0 years (males, n = 5; females, n = 6)] or S [n = 11; 81.2 ± 10.5 years (males, n = 6; females, n = 5) based on handgrip strength, body composition and physical performance. Indirect calorimetry was recorded before and after consumption of a high-CHO meal and during aerobic and anaerobic exercise. Respiratory quotient (RQ), CHO and FAT oxidation were assessed. Venous blood samples were collected for glucose and insulin concentrations.

Results: At rest, compared with NS, S exhibited a 5-8% higher RQ at 0 (0.72 vs. 0.76) and 120 (0.77 vs. 0.82), 150 (0.76 vs. 0.80), and 180 min (0.74 vs. 0.80) (P = 0.002-0.025); 59-195% higher CHO oxidation at 0, 120, and 180 min (0.0004-0.002 vs. 0.001-0.002 g·min-1 ·kg-1) (P = 0.010-0.047); and 20-31% lower FAT oxidation at 0, 15, and 90-180 min (0.0009-0.0022 vs. 0.0011-0.002 g·min-1 ·kg-1 ) (P = 0.004-0.038). Glucose levels were significantly elevated in S versus NS at 0, 60 and 75 min (144.64-202.78 vs. 107.70-134.20 mg·dL-1 ) but not insulin. During aerobic exercise, RQ was 5% greater (0.90 vs. 0.86) (P = 0.039), and FAT oxidation was 35% lower at 6-8 min (0.003 vs. 0.005 g·min-1 ·kg-1 ) (P = 0.033) in S versus NS. During anaerobic exercise, CHO oxidation was 31% greater in NS versus S at 60-80% time to exhaustion (0.011 vs. 0.007 g·min-1 ·kg-1 ) (P = 0.015). Per cent contribution to energy expenditure was greater in S for CHO but lower for FAT at 0 (CHO: 22% vs. 10%; FAT: 78% vs. 91%) and 120-180 min (CHO: 35-42% vs. 17-25%; FAT: 58-65% vs. 75%-84%) (P = 0.003-0.046) at rest and 6-8 min during aerobic exercise (CHO: 70% vs. 57%; FAT: 30% vs. 45%) (P = 0.046).

Conclusions: The data show differences in skeletal muscle energy metabolism and substrate utilization between S and NS at rest, transitioning from fasted to fed state, and during exercise. Compared with NS, S displayed a diminished ability to adapt fuel utilization in response to feeding and exercise, reflecting metabolic inflexibility. Impaired metabolic flexibility could be a mechanism underlying the losses of strength and physical function accompanying sarcopenia.

Trial registration: ClinicalTrials.gov NCT03701867.

Keywords: Ageing; Carbohydrate oxidation; Exercise; Fat oxidation; Metabolic flexibility; Metabolism; Sarcopenia.

Conflict of interest statement

SLP, JMLP and RR are employees and stock holders of Abbott. VAM is a former employee of Abbott. Since 2004, the laboratory directed by JTC has received research grants from Abbott Nutrition, National Cattlemen's Beef Association, Nebraska Beef Council, Nebraska Extension, Stepan Lipid Nutrition, Rock Creek Pharmaceuticals, General Nutrition Corporation, Experimental & Applied Sciences, Nutricia, and/or the USDA National Institute for Food and Agriculture. Between 2008 and 2018, JTC served intermittently as a paid consultant for Regeneron Pharmaceuticals, Abbott Nutrition, General Nutrition Corporation, ErgoGenix/ErgoPharm, or Corr‐Jensen Labs.

© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1

Test visit activity timeline. Resting metabolism was measured for 30 min prior to and 180 min after consuming a CHO‐rich meal. Venous blood samples (Bl) were taken fasted before the meal (baseline) and every 15 ± 5 min for the first 90 min, and then approximately every 30 ± 5 min up to 180 min.

Figure 2

Participant screening and enrolment process overview.

Figure 3

Respiratory quotient (RQ) of 11 nonsarcopenic (NS) (open circles, dashed lines) and 11 sarcopenic (S) (solid circles, solid lines) individuals (A) fasted, postprandial, and during (B) submaximal aerobic exercise and leg extensions to exhaustion. RQ was determined prior to and after consuming a CHO‐rich meal at 15‐ and 30‐min intervals, over 2‐min intervals during aerobic exercise, and over quintiles during anaerobic exercise. Differences between NS and S were determined with independent samples t‐tests. * indicates differences between groups (P ≤ 0.05). RQ was significantly higher at baseline in S and remained higher at min 120–180. During the submaximal aerobic test, S had a higher RQ than NS from min 6–8. RQ in NS continued to rise during the anaerobic fatiguing task while S had little change from steady‐state aerobic exercise to anaerobic exercise. Values are means ± 95% confidence intervals.

Figure 4

Carbohydrate (CHO) oxidation rate normalized to fat‐free mass of 11 nonsarcopenic (NS) (open circles, dashed lines) and 11 sarcopenic (S) (solid circles, solid lines) individuals (A) fasted, postprandial, and during (B) submaximal aerobic exercise and leg extensions to exhaustion. CHO oxidation was calculated for 30 min prior to and 180 min post‐consumption of a CHO‐rich meal at 15‐ and 30‐min intervals, over 2‐min intervals during aerobic exercise, and over quintiles during anaerobic exercise. Differences between NS and S were determined with independent samples t‐tests. * indicates differences between groups (P ≤ 0.05). CHO oxidation was greater in S at baseline and at min 120–180. There were no differences between the groups during aerobic exercise. During anaerobic exercise, CHO oxidation was greater in NS at 60–80% time to exhaustion compared with S. Values are means ± 95% confidence intervals.

Figure 5

FAT oxidation rate normalized to fat‐free mass of 11 nonsarcopenic (NS) (open circles, dashed lines) and 11 sarcopenic (S) (solid circles, solid lines) individuals (A) fasted, postprandial, and during (B) submaximal aerobic exercise and leg extensions to exhaustion. FAT oxidation was calculated for 30 min prior to and 180 min post‐consumption of a CHO‐rich meal at 15‐ and 30‐min intervals, over 2‐min intervals during aerobic exercise, and over quintiles during anaerobic exercise. Differences between NS and S were determined with independent samples t‐tests. * indicates differences between groups (P ≤ 0.05). At baseline and throughout the resting period, FAT oxidation was greater in NS compared with S. There were no differences between groups during exercise. Values are means ± 95% confidence intervals.

Figure 6

The percent contribution of carbohydrate (CHO) (solid lines) and FAT (dashed lines) utilization to total energy expenditure was calculated during (A) resting and (B) exercise for nonsarcopenic (NS) (top) and sarcopenic (S) individuals (bottom). The percentage of CHO and FAT contribution relative to total energy expenditure was compared between groups using independent samples t‐tests. NS showed greater contribution of fat to total energy expenditure at baseline and at 75–180 min and greater CHO oxidation at the min 6–10 of aerobic exercise and 60–100% time to exhaustion of the fatiguing bout. Less variance between CHO and FAT was seen at rest in S, while CHO oxidation was greater at min 4–10 during aerobic exercise. There were no differences between CHO and FAT contributions to substrate utilization in S. * indicates a significant difference between per cent fat and per cent CHO contributions to energy expenditure (P ≤ 0.05), and ⌘ indicates a significant difference between S and NS (P ≤ 0.05). Values are means ± 95% confidence intervals.

Figure 7

Fasting and postprandial glucose (top) and insulin (bottom) concentrations were measured before and after consumption of a CHO‐rich meal in 10 nonsarcopenic (NS) (open circles, dashed lines) and 9 sarcopenic (S) (solid circles, solid lines) individuals. Blood glucose was significantly higher in S at baseline and remained higher postprandial at 60–75 min. There were no significant differences in insulin levels between NS and S groups. Differences between NS and S were determined with independent samples t‐tests. * indicates differences between groups (P ≤ 0.05). Values are means ± 95% confidence intervals. Venous blood samples from all timepoints were unavailable for one NS participant, and one NS participant was unable to complete the blood draws at min 30 and 45. Two S participants were able to complete blood draws at 0 and 15 min but were unable to complete the rest of the blood analysis.