Abstract
Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment.
Highlights
The links between obesity and insulin resistance includes the roles of lipid deposition in non-adipose tissues, such as skeletal muscle, islets and liver [1,2], collectively called ectopic fat
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of conditions extending from simple liver steatosis to more severe liver disease such as steatohepatitis [4,5]
We present the results from clinical studies in obese adults with increased liver fat content who are treated by aggressive caloric restriction in an attempt to examine the effects on hepatic triglyceride accumulation, hepatic glucose production and peripheral glucose disposal
Summary
The links between obesity and insulin resistance includes the roles of lipid deposition in non-adipose tissues, such as skeletal muscle, islets and liver [1,2], collectively called ectopic fat. Lipotoxicity is manifested as attenuated skeletal muscle insulin sensitivity, thereby impairing its ability to take up glucose. In the liver, lipotoxicity impairs hepatic glucose metabolism by reducing its suppression of hepatic glucose production (HGP) NAFLD is highly prevalent in individuals with type 2 diabetes or/and obesity and contributes to hepatic insulin resistance. Hepatic ectopic fat is likely a critical factor modulating HGP. This is probably one reason why NAFLD has a high prevalence in type 2 diabetes and obesity
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