Adipose triacylglycerol lipase is a major regulator of hepatic lipid metabolism but not insulin sensitivity in mice.

22:01 EDT 14th September 2014 | BioPortfolio

Summary of "Adipose triacylglycerol lipase is a major regulator of hepatic lipid metabolism but not insulin sensitivity in mice."

AIMS/
HYPOTHESIS:
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.
METHODS:
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.
RESULTS:
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/
INTERPRETATION:
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.

Affiliation

Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Wellington Rd, Clayton, Victoria, 3800, Australia.

Journal Details

This article was published in the following journal.

Name: Diabetologia
ISSN: 1432-0428
Pages:

Links

PubMed Articles [15462 Associated PubMed Articles listed on BioPortfolio]

Effects of duodenal switch alone or in combination with sleeve gastrectomy on body weight and lipid metabolism in rats.

Background:A combined procedure of sleeve gastrectomy and duodenal switch (SG+DS) has been applied to the treatment of super obesity. The aim of the present study was to test whether duodenal switch a...

Defects in triacylglycerol lipolysis affect synthesis of triacylglycerols and steryl esters in the yeast.

Tgl3p, Tgl4p and Tgl5p are the major triacylglycerol lipases of the yeast S. cerevisiae catalyzing degradation of triacylglycerols stored in lipid droplets. Previous results from our laboratory (Athen...

Multi-gene engineering of triacylglycerol metabolism boosts seed oil content in Arabidopsis.

Increasing the yield of oilseed crops is an important objective for biotechnologists. A number of individual genes involved in triacylglycerol metabolism have previously been reported to enhance the o...

Regulation of lipoprotein lipase by Angptl4.

Triglyceride (TG)-rich chylomicrons and very low density lipoproteins (VLDL) distribute fatty acids (FA) to various tissues by interacting with the enzyme lipoprotein lipase (LPL). The protein angiopo...

Pathway-Selective Insulin Resistance and Metabolic Disease: The Importance of Nutrient Flux.

Hepatic glucose and lipid metabolism are altered in metabolic disease (e.g. obesity, metabolic syndrome and Type 2 diabetes). Insulin-dependent regulation of glucose metabolism is impaired. In contras...

Clinical Trials [2562 Associated Clinical Trials listed on BioPortfolio]

Genetic Epidemiology of Lipoprotein-Lipid Levels

To determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors ...

Losartan and Simvastatin in Hypertensive Obeses With Liver Steatosis

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, ...

Effects of FXR Activation on Hepatic Lipid and Glucose Metabolism

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 ...

Effects of Dietary Proteins on Hepatic Lipid Metabolism

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...

Acute Effect of Fructose on Lipid Metabolism and Gender Differences

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...

Medical and Biotech [MESH] Definitions

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 3.1.1.34.

Search BioPortfolio:
Loading