Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice.

The liver is the main organ that regulates lipid and glucose metabolism. Ectopic lipid accumulation in the liver impairs insulin sensitivity and glucose metabolism. Lipoprotein lipase (LPL), mainly expressed in the adipose tissue and muscle, is a key enzyme that regulates lipid metabolism via the hydrolysis of triglyceride in chylomicrons and very-low-density lipoproteins. Here, we aimed to investigate whether the suppression level of hepatic lipid accumulation via overexpression of LPL in mouse liver leads to improved metabolism. To overexpress LPL in the liver, we generated an LPL-expressing adenovirus (Ad) vector using an improved Ad vector that exhibited considerably lower hepatotoxicity (Ad-LPL). C57BL/6 mice were treated with Ad vectors and simultaneously fed a high-fat diet (HFD). Lipid droplet formation in the liver decreased in Ad-LPL-treated mice relative to that in control Ad vector-treated mice. Glucose tolerance and insulin resistance were remarkably improved in Ad-LPL-treated mice compared to those in control Ad vector-treated mice. The expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1, and acyl-CoA oxidase 1, were 1.7-2.0-fold higher in Ad-LPL-treated mouse livers than that in control Ad-vector-treated mouse livers. Furthermore, hepatic LPL overexpression partly maintained mitochondrial content in HFD-fed mice. These results indicate that LPL overexpression in the livers of HFD-fed mice attenuates the accumulation of lipid droplets in the liver and improves glucose metabolism. These findings may enable the development of new drugs to treat metabolic syndromes such as type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Dietary calamondin supplementation slows the progression of non-alcoholic fatty liver disease in C57BL/6 mice fed a high-fat diet.

Obesity is associated with an increased risk of metabolic abnormalities. The citrus fruit calamondin contains nobiletin and hesperidin, which are involved in lipid metabolism, and vitamin C, which is an antioxidant. We investigated the metabolic profiles of C57BL/6 mice fed a normal diet, high-fat diet (HFD), HFD + 1% (w/w) calamondin puree (HFD + CL1), or HFD + 5% (w/w) calamondin puree (HFD + CL5). Glucose tolerance was significantly higher in HFD + CL than in HFD-fed mice. Histological analysis revealed less lipid accumulation in the livers of HFD + CL-fed mice than in those of HFD-fed control mice. Hepatocyte ballooning and large lipid droplets - key non-alcoholic fatty liver disease characteristics - were observed in HFD-fed mice after 4 weeks; however, they were nearly absent in HFD + CL-fed mice. The serum expression level of inflammation-associated Ccl2 was lower in HFD + CL-fed mice than in HFD-fed mice. Thus, calamondin may ameliorate HFD-induced metabolic disturbances, including the progression of non-alcoholic fatty liver disease.