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Weight loss is the primary intervention for nonalcoholic fatty liver disease (NAFLD). A decrease in resting metabolic rate (RMR) out of proportion to the degree of weight loss may promote weight regain. We aimed to determine the impact of hepatic steatosis on weight loss‐associated changes in RMR and metabolic adaptation, defined as the difference between predicted and measured RMR after weight loss. We retrospectively analyzed prospectively collected data from 114 subjects without diabetes (52 with NAFLD), with body mass index (BMI) >35, and who enrolled in a 6‐month weight loss intervention. Hepatic steatosis was determined by unenhanced computed tomography scans by liver:spleen attenuation ratio <1.1. RMR was measured by indirect calorimetry. At baseline, patients with hepatic steatosis had higher BMI, fat mass (FM), fat‐free mass (FFM), and RMR (RMR, 1,933 kcal/day; 95% confidence interval [CI], 841‐2,025 kcal/day; versus 1,696; 95% CI, 1,641‐1,751;  P  < 0.0001). After 6 months, the NAFLD group experienced larger absolute declines in weight, FM, and FFM, but percentage changes in weight, FFM, and FM were similar between groups. A greater decline in RMR was observed in patients with NAFLD (−179 kcal/day; 95% CI, −233 to −126 kcal/day; versus −100; 95% CI, −51 to −150;  P  = 0.0154) for the time × group interaction, and patients with NAFLD experienced greater metabolic adaptation to weight loss (−97 kcal/day; 95% CI, −143 to −50 kcal/day; versus −31.7; 95% CI, −74 to 11;  P  = 0.0218) for the prediction × group interaction. The change (Δ) in RMR was significantly associated with ΔFM, ΔFFM, and baseline RMR, while metabolic adaptation was significantly associated with female sex and ΔFM only.  Conclusion:  Hepatic steatosis is associated with a greater reduction in FM, which predicts RMR decline and a higher metabolic adaptation after weight loss, potentially increasing the risk of long‐term weight regain.

Impact of Hepatic Steatosis on Resting Metabolic Rate and Metabolic Adaptation in Response to Intentional Weight Loss