Adipose tissue redistributes during aging resulting in increased intermuscular adipose tissue (IMAT), intramuscular, and intramyocellular lipid while subcutaneous fat decreases. IMAT has been associated with lower muscle strength, power, and quality, chronic inflammation, impaired glucose tolerance, and elevated total cholesterol in older adults. This review focused on trials investigating the role of age, physical activity and diet on IMAT. The studies agreed that IMAT increases with age and seems to be responsive to physical activity, particularly the combination of aerobic and resistance exercise. However, some reported this could occur with or without weight loss, and some reported that high IMAT at baseline may blunt the muscle quality adaptive response to physical training. Larger and longer trials are needed to differentiate the independent or synergistic effects of resistance and/or aerobic training, and obesity and weight loss combined with resistance, aerobic or combination of aerobic and resistance training on IMAT.
The loss of skeletal muscle mass and function with aging (i.e., sarcopenia) is a well-known biological phenomenon. These losses are accompanied by shifts in adipose tissue and accumulation of fat in other non-adipose depots. The main anatomical depots for adipocytes are subcutaneous fat (SQF), visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), intramuscular (IMC), intramyocellular lipid (IMCL), and bone marrow.
Advancing age results in a redistribution of fat, with IMAT, IMC (fat within muscle but between fibers), and IMCL tending to increase, whereas SQF decreases.
The cellular origins of adipose accumulation within muscle fibers (intramuscular IMC/IMCL) may arise directly via the accumulation of lipid within myofibers, or intramyocellular lipid.
It has also been suggested that stem cells of the skeletal muscle may be among the drivers of adipocyte accumulation in ectopic regions. Satellite cells are a well-described stem cell population in skeletal muscle. Another stem cell type has also been described more recently, known as fibro/adipogenic progenitors, or mesenchymal interstitial cells.
Inter- and intramuscular fat mass have been associated with lower muscle strength, power, and quality;
Both intra- and intermuscular fatty infiltration in skeletal muscle decrease sensitivity to insulin, which is required for normal protein synthesis.
A number of trials have investigated the roles of age, physical activity, and diet on IMAT, and a summary of these trials is presented in
To summarize these studies, Goodpaster et al.
Other interesting findings include those of Tuttle et al.
Studies to date consistently show that IMAT increases with age and appears to be responsive to physical activity, particularly the combination of aerobic and resistance exercise. However, there is less agreement regarding whether this response may occur with or without weight loss. Many of the studies cited in this brief review had small study samples. The two larger trials
The researcher claims no conflicts of interest.
Summary of studies between 2008–2017 on factors affecting IMAT
Research topic, participants | Study design, methods, outcome measures | Results | Conclusion | Investigators |
---|---|---|---|---|
Physical activity |
RCT (PA or ED) 12 month. IMAT from mid-thigh CT. | Muscle strength decreased in ED, but maintained in PA. No significant increase in IMAT in PA. SQF no difference between groups. | PA can prevent loss of strength and IMAT accumulation. | Goodpaster et al. |
Race and obesity |
BMI, DXA, SQF, and pQCT of calf muscle. | Afro-Caribbeans had greater IMAT and lower SQF at all levels of adiposity. |
IMAT greater among African than Caucasian men despite lower adiposity. IMAT associated with T2D in both groups. | Miljkovic et al. |
Aging and weight gain |
Health ABC cohort study. Thigh CT scan, CSA muscle, strength, muscle quality. | Weight gain did not prevent loss of muscle strength. IMAT increased with age in men and women. IMAT increased with weight gain, loss, or weight stability. | Aging associated with decreased strength and quality regardless of body weight changes. IMAT changes independent of weight changes. | Delmonico et al. |
Age and eccentric resistance exercise |
Two aims. Observe IMAT change with age and 3 nonconsecutive days/wk for 12-week eccentric resistance training (age 55 and over). Thigh MRI. | Increasing IMAT with age. |
Eccentric resistance training decreased thigh IMAT in a range of adults with metabolic and mobility deficits. | Marcus et al. |
Exercise and muscle location |
IMAT right calf by MRI, 6 min. walk test and PPT. | Gastrocnemius muscle highest IMAT and volume. No group differences. Calf IMAT inversely related to 6 min walk and PPT. | Calf IMAT muscle specific and associated with poorer physical performance. | Tuttle et al. |
Weight loss and physical function |
RCT comparing PA plus weight loss (PA+WL) or PA plus successful aging education (PA+SA) program. |
6 months, PA+WL lost greater thigh fat and muscle area; PA+WL lost 12.4% strength; PA+SA lost 1.0%. Muscle fat infiltration decreased significantly in PA+WL. Thigh fat area decreased 6-fold compared to lean area in PA+WL. Change in SPPB inversely correlated with change in fat, but not with change in lean or strength. | Weight loss resulted in additional functional improvements over exercise alone, primarily due to loss of body fat. | Santanasto et al. |
70 older adults with fall history |
Resistance, endurance, and balance exercise 3 nonconsecutive days/wk for 12 weeks. |
No significant changes in lean or IMAT in any group with training. MQ increased only in baseline low IMAT group. Middle and high IMAT groups did not demonstrate a significant change in MQ following training. | High thigh IMAT blunted the adaptive MQ response to training. | Yoshida et al. |
Dietary restriction and exercise (DR+E) in obese older adults |
RCT 6 months DR+E or ED. |
DR+E significantly reduced body mass. Thigh and calf muscle volumes responded similarly between groups. Knee extension strength not changed by DR+E, but trend increased walking speed in the DR+E group. DR+E reductions in SQF and IMAT within calf, but not the thigh, associated with faster walking speed. | DR+E preserved lower extremity muscle size and function and reduced regional lower extremity adipose tissue. Reductions in calf SQF and IMAT associated with positive adaptations in physical function. | Manini et al. |
CR for weight loss and RT on muscle and physical function |
RCT of 5-month progressive, 3 d/wk, moderate-intensity RT with weight loss (RT+CR) or RT without weight loss (RT). |
Fat mass, % fat, and all thigh fat volumes decreased in both groups. Only RT+CR group lost lean mass. Post-intervention body and thigh composition were all lower with RT+CR except IMAT. |
RT improved body composition (including reduced IMAT) and muscle strength and physical function. Higher baseline adiposity had less improvement. | Nicklas et al. |
PA and weight loss. |
12-month pilot RCT |
Decreased IMAT and VAT significantly associated with improved SPPB independent of change in total fat mass. PA+WL improved SPPB, whereas PA+SA did not. No intergroup differences. | Decreases in IMAT and VAT important mechanisms underlying improved function following intentional weight loss plus physical activity. | Santanasto et al. |
Nutritional supplementation and physical activity. |
Six-month trial. All participated in a PA program of walking, lower-extremity strength exercises, balance, and flexibility. |
Both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation led to further losses of IMAT and increased normal muscle density. | Six months of physical activity resulted in improvements in body composition, SQF, IMAT and strength. Addition of nutritional supplement showed further declines in IMAT and improved muscle density. | Englund et al. |
IMAT, intermuscular adipose tissue; RCT, randomized controlled trial; PA, physical activity; ED, education; CT, computed tomography; SQF, subcutaneous fat; BMI, body mass index; DXA, dual energy X-ray absorptiometry; pQCT, peripheral quantitative computed tomography; T2D, type 2 diabetes; ABC, aging and body composition; CSA, cross sectional area; MRI, magnetic resonance spectroscopy; PPT, physical performance test; WL, weight loss; SA, successful aging; SPPB, short physical performance battery; MVC, maximal voluntary contraction; MQ, muscle quality; DR, dietary restriction; E, exercise; RT, resistance training; CR, caloric restriction; VAT, visceral adipose tissue.