Hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) but lifestyle modifications, such as caloric restriction (CR), can prevent these conditions. PURPOSE: We sought to determine if prior CR had protective effects on metabolic health and NAFLD development following a 4 week return to ad libitum (AL) feeding. METHODS: Four-week old male OLETF rats (n=8-10/group) were fed AL for 16 weeks (O-AL), CR for 16 weeks (O-CR; ~70% kcal of O-AL), or CR for 12 weeks followed by 4 weeks of AL feeding (O-AL4wk). RESULTS: CR-induced benefits in the prevention of NAFLD, including reduced hepatic steatosis, inflammation, and markers of Kupffer cell activation/number, were largely lost in AL4wk rats. These findings occurred in conjunction with a partial loss in CR-induced benefits on obesity and serum triglycerides in O-AL4wk but in the absence of changes in serum glucose or insulin. CR-induced increases in hepatic mitochondrial respiration remained significantly elevated (p<0.01) in O-AL4wk rats compared with O-AL rats, while mitochondrial [1-14C] palmitate oxidation, citrate synthase activity, and β-HAD activity did not differ among OLETF groups. NAFLD development in O-AL4wk rats was accompanied by increases in the protein content of the de novo lipogenesis markers FAS and SCD-1, and decreases in pACC/ACC vs O-CR (p<0.05 for each). CONCLUSION: The beneficial effects of chronic CR on NAFLD development were largely lost with 4 weeks of ad libitum feeding in the hyperphagic OLETF rat, highlighting the importance of maintaining energy balance in the prevention of NAFLD.
- caloric restriction
- hepatic steatosis
- de novo lipogenesis
- Copyright © 2016, American Journal of Physiology- Gastrointestinal and Liver Physiology