Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function

Abstract

Objective: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures.

Methods and procedures: Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood.

Results: At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation.

Discussion: CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

Figure 1

Relation between intrahepatic lipid (IHL) measured by magnetic resonance spectroscopy (MRS) and the ratio of the attenuation (in Hounsfield units (HU)) of liver tissue relative to spleen tissue (liver-to-spleen ratio) (in HU) measured by computed tomography (CT) (P < 0.05). A lower liver-to-spleen ratio reflects a higher lipid content. Data are shown for the group of white men (open triangles), white women (open circles), black men (black triangles), and black women (black circles).

Figure 2

Liver lipid stores at baseline and after 6 months of treatment with caloric restriction (CR), caloric restriction and increased structured exercise (CR+EX), a low-calorie diet (LCD) or control (see text for treatment details) assessed by (a) magnetic resonance spectroscopy and (b) computed tomography. For (a) intrahepatic lipid (IHL), values at 6 months are significantly different than baseline for all treatment groups (CR, CR+EX, and LCD). *Significantly different from control; ^†significantly different from baseline.