Differential expression of genes associated with lipid metabolism in longissimus dorsi of Korean bulls and steers.

The objective of this study was to compare expression of genes associated with lipid deposition and removal between bulls and steers in the longissimus dorsi muscle (LM) tissue of Korean cattle. Castration increased the expression of lipid uptake lipoprotein lipase, fatty acid translocase, and fatty acid transport protein 1 in LM. Castration increased lipogenic gene expression of both acetyl-CoA carboxylase and fatty acid synthase. In contrast, castration downregulated lipolytic gene expression of both adipose triglyceride lipase (ATGL) and monoglyceride lipase. Steers showed higher expression levels of insulin signaling phospho-v-akt murine thymoma viral oncogene homolog 1 than bulls but lower protein levels of nuclear Forkhead box O 1 (FoxO1) than bulls, suggesting that increased insulin signaling following castration decreases nuclear FoxO1 levels, leading to downregulation of ATGL gene expression. These findings suggest that castration contributes to increases in lipid uptake and lipogenesis and a decrease in lipolysis, resulting in improved marbling.

Dietary protein restriction induces steatohepatitis and alters leptin/signal transducers and activators of transcription 3 signaling in lactating rats.

Dietary protein restriction during lactation affects lipid metabolism and food intake in rats. The goals of this study were to determine the effect of a low-protein diet on a liver damage in lactating rats, to determine whether dietary protein restriction of lactating dams affects the liver health of their offspring and to elucidate the molecular mechanisms underlying the development of hepatic damage. Lactating Sprague-Dawley rats were fed either a control 20% protein diet or an 8% low-protein diet for 11 or 23 days, respectively. After weaning, the offspring were continuously fed either the same control diet or the low-protein diet for an additional 22 days. Feeding a low-protein diet during lactation caused steatohepatitis with severe steatosis, lobular inflammation, ballooning degeneration and fibrosis. Offspring nourished by dams fed a low-protein diet showed simple hepatic steatosis. Combined effects of increased lipogenesis, decreased fatty acid oxidation and impaired very-low-density lipoprotein secretion were responsible for the development of hepatic steatosis. Hepatic up-regulation of genes linked to oxidative stress including nicotinamide adenine dinucleotide phosphate oxidase, inflammation and fibrogenesis supports the development of steatohepatitis in protein-restricted lactating rats. Furthermore, protein-restricted lactating rats showed activation of the leptin/signal transducers and activators of the transcription 3 signaling pathway. Taken together, oxidative stress induced by up-regulation of nicotinamide adenine dinucleotide phosphate oxidase with activation of leptin/signal transducers and activators of the transcription 3 signaling was responsible for development of steatohepatitis in protein-restricted lactating rats. Our findings suggest that protein malnutrition has a potential to induce steatohepatitis/hepatic steatosis in lactating mothers and infants during breast-feeding.

Effect of L-carnitine on skeletal muscle lipids and oxidative stress in rats fed high-fructose diet.

There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR) on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet) displayed decreased glucose/insulin (G/I) ratio and insulin sensitivity index (ISI(0,120)) indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic and nonenzymic antioxidants. Simultaneous intraperitoneal administration of CAR (300 mg/kg/day) to fructose-fed rats alleviated the effects of fructose. These rats showed near-normal levels of the parameters studied. The effects of CAR in this model suggest that CAR supplementation may have some benefits in patients suffering from insulin resistance.

Fructose-induced hepatic gluconeogenesis: effect of L-carnitine.

High fructose feeding (60 g/100 g diet) in rodents induces alterations in both glucose and lipid metabolism. The present study was aimed to evaluate whether intraperitoneal carnitine (CA), a transporter of fatty acyl-CoA into the mitochondria, could attenuate derangements in carbohydrate metabolizing enzymes and glucose overproduction in high fructose-diet fed rats. Male Wistar rats of body weight 150-160 g were divided into 4 groups of 6 rats each. Groups 1 and 4 animals received control diet while the groups 2 and 3 rats received high fructose-diet. Groups 3 and 4 animals were treated with CA (300 mg/Kg body weight/day, i.p.) for 30 days. At the end of the experimental period, levels of carnitine, glucose, insulin, lactate, pyruvate, glycerol, triglycerides and free fatty acids in plasma were determined. The activities of carbohydrate metabolizing enzymes and glycogen content in liver and muscle were assayed. Hepatocytes isolated from liver were studied for the gluconeogenic activity in the presence of substrates such as pyruvate, lactate, glycerol, fructose and alanine. Fructose-diet fed animals showed alterations in glucose metabolizing enzymes, increased circulating levels of gluconeogenic substrates and depletion of glycogen in liver and muscle. There was increased glucose output from hepatocytes of animals fed fructose-diet alone with all the gluconeogenic substrates. The abnormalities associated with fructose feeding such as increased gluconeogenesis, reduced glycogen content and other parameters were brought back to near normal levels by CA. Hepatocytes from these animals showed significant inhibition of glucose production from pyruvate (74.3%), lactate (65.4%), glycerol (69.6%), fructose (56.2%) and alanine (63.6%) as compared to CA untreated fructose-fed animals. The benefits observed could be attributed to the effect of CA on fatty acyl-CoA transport.