Long-lasting improvements in liver fat and metabolism despite body weight regain after dietary weight loss

Sven Haufe, Verena Haas, Wolfgang Utz, Andreas L Birkenfeld, Stephanie Jeran, Jana Böhnke, Anja Mähler, Friedrich C Luft, Jeanette Schulz-Menger, Michael Boschmann, Jens Jordan, Stefan Engeli, Sven Haufe, Verena Haas, Wolfgang Utz, Andreas L Birkenfeld, Stephanie Jeran, Jana Böhnke, Anja Mähler, Friedrich C Luft, Jeanette Schulz-Menger, Michael Boschmann, Jens Jordan, Stefan Engeli

Abstract

Objective: Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known.

Research design and methods: We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17-36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance.

Results: Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline.

Conclusions: A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions.

Trial registration: ClinicalTrials.gov NCT00956566.

Figures

Figure 1
Figure 1
BMI, abdominal fat, and intrahepatic fat after 6-month diet and at follow-up. Changes in BMI and subcutaneous abdominal adipose tissue (AT) (upper panel) and visceral AT and intrahepatic lipids (lower panel) in 50 overweight and obese subjects. Magnetic resonance studies were performed at baseline, after a 6-month hypocaloric diet, and at long-term follow-up. *P < 0.01 compared with baseline. †P < 0.01 compared with end of diet. Group comparison by one-way ANOVA for repeated measures with Bonferroni post hoc test. Data are mean ± SEM.
Figure 2
Figure 2
Glucose and insulin concentrations during OGTT after 6-month diet and at follow-up. Time course and areas under the curve (AUC) for glucose (upper panel) and insulin (lower panel) during a 2-h OGTT (n = 46). The test was performed at baseline, after a 6-month hypocaloric diet, and at long-term follow-up. *P < 0.01 compared with baseline. Group comparison by one-way ANOVA for repeated measures and Bonferroni post hoc test. Data are mean ± SEM.

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