Track topics on Twitter Track topics that are important to you
Hepatic steatosis is characterised by excessive triacylglycerol accumulation and is strongly associated with insulin resistance. An inability to efficiently mobilise liver triacylglycerol may be a key event mediating hepatic steatosis. Adipose triacylglycerol lipase (ATGL) is a key triacylglycerol lipase in the liver and we hypothesised that liver-specific overproduction of ATGL would reduce steatosis and enhance insulin action in obese rodents.
Studies of fatty acid metabolism were conducted in primary hepatocytes isolated from wild-type and Atgl (also known as Pnpla2)(-/-) mice. An ATGL adenovirus was utilised to overproduce ATGL in the livers of obese insulin-resistant C57Bl/6 mice (Ad-ATGL). Blood chemistry, hepatic lipid content and insulin sensitivity were assessed in mice.
Triacylglycerol content was increased in Atgl (-/-) hepatocytes and was associated with increased fatty acid uptake and impaired fatty acid oxidation. ATGL adenovirus administration in obese mice increased the production of hepatic ATGL protein and reduced triacylglycerol, diacylglycerol and ceramide content in the liver. Overproduction of ATGL improved insulin signal transduction in the liver but did not affect fasting glycaemia or insulinaemia. Inflammatory signalling was not suppressed by ATGL overproduction. While ATGL overproduction increased plasma non-esterified fatty acids, neither lipid deposition nor insulin-stimulated glucose uptake were affected in skeletal muscle. CONCLUSIONS/
Liver ATGL overproduction decreases hepatic steatosis and mildly enhances liver insulin sensitivity. These effects are not sufficient to improve fasting glycaemia or insulinaemia in rodent obesity.
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Wellington Rd, Clayton, Victoria, 3800, Australia.
This article was published in the following journal.
Adipose Triglyceride Lipase (ATGL) performs the first and rate-limiting step in lipolysis by hydrolyzing triacylglycerols stored in lipid droplets to diacylglycerols. By mediating lipolysis in adipose...
Several studies have demonstrated that a high-fructose (FRUC) diet induces metabolic and haemodynamic abnormalities, known as the metabolic syndrome, which are characterised by obesity, glucose intole...
: Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metaboli...
Methionine restriction (MR) exerts many beneficial effects, such as increasing longevity, decreasing oxidative damage and alleviating inflammatory responses. Much attention has been recently focused o...
Diatoms accumulate triacylglycerols (TAGs) as storage lipids, but the knowledge about the molecular mechanisms of lipid metabolism is still sparse. Starting from a partial sequence for a putative TAG-...
To determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors ...
Angiotensin II has been proposed as a lipid metabolism regulator. It is known that adipocytes secrete a variety of protein, such as TNFα, plasminogen activator inhibitor (PAI)-1, leptin, ...
The purpose of this study is to determine whether chenodeoxycholic acid decreases de novo hepatic lipogenesis, hepatic fat content, hepatic triglyceride production and plasma triglyceride ...
Individuals submitted to a high-fat or a high-fructose/sucrose diet develop, over a 6 day-period, several features of the metabolic syndrome, including increased plasma triglycerides, incr...
It has been widely documented that fructose overfeeding increases plasma triglycerides and hepatic de novo lipogenesis, and impairs insulin sensitivity in healthy male volunteers. The effe...
The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.
Compounds that increase the enzymatic activity of LIPOPROTEIN LIPASE. Lipoprotein lipase activators have a potential role in the treatment of OBESITY by increasing LIPID METABOLISM. Note that substances that increase the synthesis of lipoprotein lipase are not included here.
A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS. It contains a cofactor for LIPOPROTEIN LIPASE and activates several triacylglycerol lipases. The association of Apo C-II with plasma CHYLOMICRONS; VLDL, and HIGH-DENSITY LIPOPROTEINS is reversible and changes rapidly as a function of triglyceride metabolism. Clinically, Apo C-II deficiency is similar to lipoprotein lipase deficiency (HYPERLIPOPROTEINEMIA TYPE I) and is therefore called hyperlipoproteinemia type IB.
LIPOLYSIS of stored LIPIDS in the ADIPOSE TISSUE to release FREE FATTY ACIDS. Mobilization of stored lipids is under the regulation of lipolytic signals (CATECHOLAMINES) or anti-lipolytic signals (INSULIN) via their actions on the hormone-sensitive LIPASE. This concept does not include lipid transport.
An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 126.96.36.199.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Obesity is the condition in which excess fat has accumulated in the body (mostly in subcutaneous tissues). clinical obesity is considered to be present when a person has a BMI of over 30 (Oxford Dictionary of Medicine). It is becoming increasing common i...