Racial differences in fat distribution: the importance of intermuscular fat

¹ From the Division of Musculoskeletal Imaging (MT) and the Program in Nutritional Metabolism (SG), Massachusetts General Hospital and Harvard Medical School, Boston, MA.

² Address reprint requests to S Grinspoon, Program in Nutritional Metabolism, Massachusetts General Hospital, 55 Fruit Street, LON207, Boston, MA 02114. E-mail: sgrinspoon{at}partners.org.

See corresponding article on page 903.

The anatomic distribution of adipose tissue is an important determinant of metabolic and cardiovascular disease risk. In particular, attention has focused traditionally on the accumulation of visceral adipose tissue (VAT) as a stronger independent predictor of insulin resistance than the accumulation of subcutaneous adipose tissue (SAT) (1). However, the degree of adipose accumulation in the visceral compartment may tell only part of the story. For example, cardiovascular disease risk is elevated in African Americans despite a lower relative accumulation of VAT, which suggests the importance of other fat depots or mechanisms mediating risk in this population (2). Recently, attention has focused on the relative distribution of lipids and adipose tissue in the extremities as being an important factor modulating the response of skeletal muscle to insulin. At the intramyocellular level, accumulation of fatty acid metabolites (triacylglycerols, diacylglycerol, and fatty acyl CoAs) results in decreased glucose transport through deficient activation of the PI 3-kinase cascade (3). Magnetic resonance (MR) spectroscopy is the only noninvasive technique capable of measuring intramyocellular lipids (IMCLs), and several studies have shown strong correlations between IMCL concentrations and insulin resistance in obese persons, persons with HIV-lipodystrophy, and offspring of persons with type 2 diabetes (4).

Furthermore, it has become apparent from lipodystrophic patients and animal models that subcutaneous fat is critically necessary as a storage depot for energy substrate. Too little subcutaneous fat is as much a problem as is too much subcutaneous fat. In animal models, lack of subcutaneous fat is associated with severe insulin resistance. Transplantation of subcutaneous fat with intact leptin-producing genes is associated with the reversal of insulin resistance and dyslipidemia and decreased hepatic steatosis (5). IMCL concentrations are elevated in lipodystrophic patients, possibly as a spillover phenomenon, which contributes to insulin resistance (6). Drugs, such as the thiazolidinediones, may reduce visceral fat and increase subcutaneous fat and could be useful in modulating cardiovascular disease risk (7), but further research is needed before thiazolidinediones can be used for this purpose.

Interestingly, the accumulation of adipose tissue surrounding muscle bundles (intermuscular adipose tissue; IMAT) also has a strong association with insulin resistance. Using computed tomography, Goodpaster et al (8) originally described the IMAT compartment in the thigh, showing a negative association with insulin sensitivity in lean and obese glucose-tolerant subjects and obese subjects with diabetes mellitus. Although the mechanism of this effect is unknown, it is possible that IMAT affects peripheral insulin dynamics by impairing muscle blood flow, reducing insulin diffusion capacity, increasing local concentrations of fatty acids, or enhancing rates of lipolysis within skeletal muscle (8). On the other hand, muscle attenuation measured from a region of interest on a single computed tomography slice (eg, psoas, midthigh) expresses a combination of IMAT and IMCL, which decreases as a function of overall muscle adiposity. This technique has been successfully used in previous studies and has shown a strong correlation with insulin sensitivity (8, 9).

In this issue of the Journal, Gallagher et al (10) present the results of a cross-sectional study using whole-body MR imaging to selectively quantify IMAT in relation to age, sex, ethnicity, and overall adiposity. A total of 338 sedentary men and women (118 African Americans, 51 Asians, and 169 whites) were examined. At low levels of total adiposity, African Americans, Asians, and whites had comparable amounts of adjusted IMAT. However, with increasing total adiposity, African Americans had the greatest increment in IMAT per kilogram of total fat among the 3 groups. Conversely, increasing total adiposity resulted in greater increments of VAT than of IMAT in whites and Asians than in African Americans, whereas the rates of increase in VAT and IMAT were parallel and did not differ significantly in African Americans. A rigorous technique was used to determine IMAT. All MR scans were read by one reader, who was presumably blinded to demographic data. Nonetheless, the variability of the IMAT measurement was somewhat higher than that for SAT or VAT, and relative differences in IMAT between racial groups must be considered within the degree of demonstrated precision of the technique; eg, small differences (<5.9%) may not be detectable.

There is growing evidence that race-related variations in fat depots lead to differential effects on insulin sensitivity. In a study of obese African American and white adolescents, Bacha et al (2) observed that VAT was 30% lower in the African Americans, despite nonsignificant differences in BMI, total and percentage body fat, and peripheral insulin sensitivity between the 2 groups. On the other hand, no significant differences in cardiovascular disease risk and lipid profiles were observed between African American subjects with low amounts of VAT and those with high amounts of VAT (2). This raises an important question: do fat depots other than VAT and SAT affect glucose homeostasis and metabolic and cardiovascular disease risk in specific racial groups?

The current study provides important new information on racial differences in the size and relation of the IMAT compartment to total and visceral fat. These data suggest, but do not prove, that IMAT may contribute to racial differences in cardiovascular disease risk and insulin resistance. A limitation of the current study by Gallagher et al is the lack of any information on metabolic factors, such as insulin, glucose, or lipids. In addition, no data are provided on dietary or physical activity. Of importance was that BMI differed significantly between the racial groups. Adjustment for weight in regression modeling may not be adequate to account for large differences in weight between study populations. The relation of IMAT to VAT or to total adiposity may differ in overweight and normal-weight racial groups. Future studies will need to compare IMAT, SAT, VAT, and IMCL between races in relation to metabolic markers. In addition, longitudinal studies to compare rates of change in metabolic variables over time are also needed. The study by Gallagher et al should prompt further studies to delineate the important roles played by inter- and intramuscular fat in mediating metabolic risk across different populations.

ACKNOWLEDGMENTS

The author had no conflict of interest but was a coinvestigator with Jeanine Albu on an unrelated project.

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Related articles in AJCN:

Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue

Dympna Gallagher, Patrick Kuznia, Stanley Heshka, Jeanine Albu, Steven B Heymsfield, Bret Goodpaster, Marjolein Visser, and Tamara B Harris
AJCN 2005 81: 903-910. [Full Text]