The Effect of the Short‐Term Growth Hormone Administration on Non‐Alcoholic Fatty Liver Disease in Diet‐Induced Obesity Models

Abstract

Non‐alcoholic fatty liver disease (NAFLD) is one of the characteristics of metabolic syndrome. Most people are facing NAFLD whether they are diagnosed with obesity or not. Additionally, growth hormone (GH) administration could mediate the storage of body fat, including in the liver, as a result of the lipolytic effect. In obese patients, the reduction of GH level has been reported. The long‐term treatment of obesity with GH has been shown to reduce body fat mass as well as its well‐known effect to counteract insulin action, leading to insulin resistance. However, this remains unknown whether the short‐term GH administration can alter the fat storage in the liver while it does not worsen insulin sensitivity. To investigate this hypothesis, the rats were fed with either high‐fat (HF) or standard diet for 6 weeks, resulting in diet‐induced obesity (DIO) or diet‐resistant (DR) rats. The effect of short‐term GH treatment (1 mg/kg, twice daily, subcutaneous injection) was then assessed and compared to saline treatment after 3‐day of GH administration. A glucose tolerance test was performed after GH treatment to assess insulin sensitivity in vivo. After euthanasia, the liver was weighed and collected to measure triglyceride concentration by colorimetric assay. Blood was also collected to determine plasma free fatty acid (FFA) levels for the measurement of the lipolytic activity of GH. The results revealed that the percentage of liver mass was significantly greater in DIO and DR rats compared to control rats (p<0.05). The short‐term GH administration did not alter the percentage of liver weight. For liver triglyceride level, DIO and DR rats had a higher level than that of control rats (p<0.05); however, the liver triglyceride level did not affect by the short‐term GH treatment in all rats. Interestingly, the short‐term GH administration significantly increased plasma FFA only in DR rats (p<0.05). Moreover, the effect of GH significantly improved glucose tolerance especially in DIO rats (p<0.01), whereas it did not significantly affect insulin sensitivity in control and DR rats. Taken together, this study suggested that the short‐term GH administration may influence liver lipid metabolism in DR rats. However, further studies are required to determine whether short‐term GH administration affected liver lipid metabolism by interfering with the gene expression, including lipid uptake, lipid synthesis, and lipid oxidation. Additionally, the mechanisms underlying the effect of the short‐term GH administration on insulin sensitivity remains the subject for further studies.