Ethnic differences in hepatic steatosis: an insulin resistance paradox?

Abstract

Nonalcoholic fatty liver disease is a burgeoning problem. We have previously shown that Hispanics were at greater risk for nonalcoholic fatty liver disease than were African-Americans despite a similar prevalence of risk factors between these groups. We have performed the largest, population-based study to date (n = 2170) utilizing proton magnetic resonance (MR) spectroscopy, dual-energy x-ray absorptiometry, and multislice abdominal MR imaging to determine the contribution of body fat distribution to the differing prevalence of hepatic steatosis in the three major U.S. ethnic groups (African-American, Hispanic, Caucasian). Despite controlling for age and total adiposity, African-Americans had less intraperitoneal (IP) fat and more lower extremity fat than their Hispanic and Caucasian counterparts. The differences in hepatic triglyceride content (HTGC) between these groups remained after controlling for total, abdominal subcutaneous, and lower extremity adiposity; however, controlling for IP fat nearly abolished the differences in HTGC, indicating a close association between IP and liver fat regardless of ethnicity. Despite the lower levels of IP and liver fat in African-Americans, their prevalence of insulin resistance was similar to Hispanics, who had the highest levels of IP and liver fat. Furthermore, insulin levels and homeostasis model assessment values were highest and serum triglyceride levels were lowest among African-Americans after controlling for IP fat.

Conclusion: IP fat is linked to HTGC, irrespective of ethnicity. The differing prevalence of hepatic steatosis between these groups was associated with similar differences in visceral adiposity. The metabolic response to obesity and insulin resistance differs in African-Americans when compared to either Hispanics or Caucasians: African-Americans appear to be more resistant to both the accretion of triglyceride in the abdominal visceral compartment (adipose tissue and liver) and hypertriglyceridemia associated with insulin resistance.

Figures

Figure 1. Comparisons of the Distribution of Intraperitoneal, Abdominal Subcutaneous, and Lower Extremity Fat Between Hispanics, African-Americans, and Caucasians

* indicates values are significantly different from African-Americans within the gender group (P<0.01).

Figure 2. Relationship Between Hepatic Triglyceride Content and Total/Regional Adiposity

Hepatic triglyceride content (HTGC) was log transformed to meet assumptions of ANCOVA analysis. As expected, HTGC increased as a function of total and regional adiposity in all groups, but this relationship varied by ethnicity. (A) The plot of HTGC vs. percent body fat (%BF) in men and women. In Hispanic and Caucasian men, the difference in slopes of this relationship was not significant (P=0.539); however, the slope of this relationship trended toward lower values in African-American men compared to the other ethnicities (vs. Hispanic, P=0.067; vs. Caucasian, P=0.054). Hispanics had the highest mean value of HTGC followed by Caucasian then African-American men after adjustment for %BF (P<0.033). Among the women, all ethnicities demonstrated different slopes for this relationship (P<0.025). The greatest slope was observed in Hispanic women followed by Caucasian then African-American women. (B) The plot of HTGC vs. percent intraperitoneal fat (%IP) (intraperitoneal fat mass / total body mass) in men and women. All regression lines had equal slopes and the ethnic-specific adjusted mean values of HTGC were similar among the men (Hispanics 4.2±1.0 vs. Caucasians 3.8±1.0 vs. African-Americans 3.5±1.0 %, P>0.05 for all comparisons). Among the women, all regression lines had equal slopes. The adjusted mean value of HTGC was similar between Hispanic and African-American women once adjusted for %IP (3.9±1.1 vs. 3.5±1.0 %, respectively; P=0.260). However, the mean value of HTGC in Caucasian women was slightly lower than the other ethnicities after adjustment for %IP (3.0±1.1 %, P<0.01). Adjusting HTGC for subcutaneous and lower extremity fat failed to account for the difference in HTGC between these ethnic groups. Indeed, adjustment for subcutaneous fat yielded results similar to adjustment for %BF. Likewise, the slope of the relationship between HTGC and lower extremity fat either approached zero (men) or was not significantly different from zero (women).

Figure 3. Relationship Between Hepatic Triglyceride Content and Total/Regional Adiposity by Gender

Hepatic triglyceride content (HTGC) was log transformed to meet assumptions of ANCOVA analysis. As expected, HTGC increased as a function of total and regional adiposity in both sexes. (A) The plot of HTGC vs. percent body fat (%BF) in men and women. The slopes of this relationship were significantly different (Slope Men 0.06 vs. Slope women 0.05 P=0.019). (B) The plot of HTGC vs. percent intraperitoneal fat (%IP) (intraperitoneal fat mass / total body mass) in men and women. The slopes of this relationship were significantly different (Slope Men 0.66 vs. Slope women 0.81 P=0.022). Adjustment for subcutaneous fat yielded results similar to adjustment for %BF.

Figure 4. Relationship Between Insulin Resistance, Intraperitoneal Adiposity, Hepatic Triglyceride Content and Plasma Triglyceride Levels

(A) The plot of HOMAIR vs. %IP in men and women. Among the men, all regression lines had equal slopes. The mean value of HOMAIR was higher in African-American men after adjustment for %IP (P<0.023), while Hispanic and Caucasian men had similar mean HOMAIR values after this adjustment (P=0.138). Among the women, all regression lines had equal slopes. After adjustment for %IP, African-American women had the highest values of HOMAIR followed by Hispanic then Caucasian women (P<0.001). (B) The plot of serum triglyceride (TG) vs. hepatic triglyceride content (HTGC) in men and women. The slope of the relationship between HTGC and TG in African-American men was significantly lower than the other men (P<0.001). No difference in slope or mean value of TG was apparent between Hispanic and Caucasian men after adjustment for HTGC. Among the women, all regression lines had equal slopes. African-American women had lower mean TG levels after adjustment for HTGC (P<0.001). Mean TG levels remained similar between Hispanic and Caucasian women after adjustment for HTGC (P=0.878).