The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats

Obeid, OA; Powell-Tuck, J; Emery, Peter W.

doi:10.1038/sj.ijo.0801189

Cited by 18 publications

(10 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This model predicts that individuals consume food to a level that maintains glycogen levels in the body (12). In fact, many lines of experimental evidence establish a correlation between the size of liver glycogen stores and food intake (13,14); however, other results have argued against this hypothesis (15)(16)(17). The results in Yang and Newgard (9) and Ros et al (10) support the notion that liver glycogen is a factor controlling food intake in hyperphagic type 1 diabetic animals.…”

supporting

confidence: 73%

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

et al. 2014

View full text Add to dashboard Cite

We generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTG OE ), which results in an increase in liver glycogen. When fed a high-fat diet (HFD), these animals reduced their food intake. The resulting effect was a lower body weight, decreased fat mass, and reduced leptin levels. Furthermore, PTG overexpression reversed the glucose intolerance and hyperinsulinemia caused by the HFD and protected against HFD-induced hepatic steatosis. Of note, when fed an HFD, PTG OE mice did not show the decrease in hepatic ATP content observed in control animals and had lower expression of neuropeptide Y and higher expression of proopiomelanocortin in the hypothalamus. Additionally, after an overnight fast, PTG OE animals presented high liver glycogen content, lower liver triacylglycerol content, and lower serum concentrations of fatty acids and b-hydroxybutyrate than control mice, regardless of whether they were fed an HFD or a standard diet. In conclusion, liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of an HFD, and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity.Liver glycogen acts as an energy store in times of nutritional sufficiency for use in times of need. The metabolism of this polysaccharide in the liver is controlled by the activities of two key enzymes: glycogen synthase (GS) and glycogen phosphorylase (GP) (1). GS is phosphorylated at multiple sites, which induces its inactivation, whereas GP is activated by phosphorylation at a single site. Both enzymes are also regulated allosterically (2,3).Glycogen-targeting subunits bind to glycogen and protein phosphatase 1 (PP1) and facilitate the dephosphorylation of GS and GP, thus activating the former and inactivating the latter. Six genes encode glycogen-targeting subunits (4). Among these, protein targeting to glycogen (PTG) (PPP1R3C or PPP1R5), which is expressed in many tissues, has been shown to control glycogen stores in various animal models (5-7).Adenoviral PTG overexpression in the liver of normal rats increases glycogen and improves glucose tolerance without perturbing lipid metabolism (8). In a diabeticfocused approach, Yang and Newgard (9) showed that adenoviral expression of PTG in the liver of STZ-diabetic rats increased glycogen content and reversed hyperglycemia and hyperphagia. Through a different approach, we reported that hepatic adenoviral expression of an active form of liver GS (LGS), which also increases glycogen content, in STZ-diabetic rats reduced food intake and hyperglycemia (10).Russek (11) was the first to propose a hepatostatic theory of food intake, which was further redefined as a glycogenostatic model by Flatt (12). This model predicts that individuals consume food to a level that maintains glycogen levels in the body (12). In fact, many lines of experimental evidence establish a correlation between the size of liver ...

show abstract

supporting

confidence: 73%

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Our tissue fraction-specific analyses distinguished between lean and lipid tissue fractions. We were therefore able to distinguish between 13 C atoms initially attached to glucose that remained in a leancarbohydrate fraction and those that were converted into fatty acid or glycerol and were subsequently incorporated into the lipid fraction (Obeid and Emery 1997;Obeid et al 2000;GayeSiessegger et al 2004). Additional tissue separation approaches might include extraction of lean fractions with trichloroacetic acid or separation of the lipid fraction into polar and neutral components (Guglielmo et al 2002;McCue et al 2009;BenHamo et al 2011).…”

Section: Discussionmentioning

confidence: 98%

A Mass Balance Approach to Identify and Compare Differential Routing of¹³C-Labeled Carbohydrates, Lipids, and Proteins In Vivo

McCue

Smith²,

McKinney³

et al. 2011

Physiological and Biochemical Zoology

View full text Add to dashboard Cite

All animals route assimilated nutrients to their tissues where they are used to support growth or are oxidized for energy. These nutrients are probably not allocated homogeneously among the various tissue and are more likely to be preferentially routed toward some tissues and away from others. Here we introduce an approach that allows researchers to identify and compare nutrient routing among different organs and tissues. We tested this approach by examining nutrient routing in birds. House sparrows Passer domesticus were fed a meal supplemented with one of seven (13)C-labeled metabolic tracers representing three major classes of macronutrients, namely, carbohydrates, amino acids, and fatty acids. While these birds became postabsorptive (2 h after feeding), we quantified the isotopic enrichment of the lean and lipid fractions of several organs and tissues. We then compared the actual (13)C enrichment of various tissue fractions with the predictions of our model to identify instances where nutrients were differentially routed and found that different classes of macronutrients are uniquely routed throughout the body. Recently ingested amino acids were preferentially routed to the lean fraction of the liver, whereas exogenous carbohydrates were routed to the brain and the lipid fraction of the liver. Fatty acids were definitively routed to the heart and the liver, although high levels of palmitic acid were also recovered in the adipose tissue. Tracers belonging to the same class of molecules were not always routed identically, illustrating how this technique is also suited to examine differences in nonoxidative fates of closely related molecules. Overall, this general approach allows researchers to test heretofore unexamined predictions about how animals allocate the nutrients they ingest.

show abstract

“…Activation of lipogenic pathways and suppression of fatty acid oxidation are also observed in obesity (25,26). Insulin treatment or carbohydrate-rich diets upregulate hepatic mtGPAT activity in vivo (12).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis

Lindén

William-Olsson

Rhedin

et al. 2004

Journal of Lipid Research

View full text Add to dashboard Cite

Glycerol-3-phosphate acyltransferase (GPAT) catalyses the first committed step in glycerolipid biosynthesis. The mitochondrial isoform (mtGPAT) is mainly expressed in liver, where it is highly regulated, indicating that mtGPAT may have a unique role in hepatic fatty acid metabolism. Because both mtGPAT and carnitine palmitoyl transferase-1 are located on the outer mitochondrial membrane, we hypothesized that mtGPAT directs fatty acyl-CoA away from ␤ -oxidation and toward glycerolipid synthesis. Adenoviralmediated overexpression of murine mtGPAT in primary cultures of rat hepatocytes increased mtGPAT activity 2.7-fold with no compensatory effect on microsomal GPAT activity. MtGPAT overexpression resulted in a dramatic 80% reduction in fatty acid oxidation and a significant increase in hepatic diacylglycerol and phospholipid biosynthesis. Following lipid loading of the cells, intracellular triacylglycerol biosynthesis was also induced by mtGPAT overexpression. Changing an invariant aspartic acid residue to a glycine [D235G] in mtGPAT resulted in an inactive enzyme, which helps define the active site required for mammalian mtGPAT function. To determine if obesity increases hepatic mtGPAT activity, two models of rodent obesity were examined and shown to have Ͼ 2-fold increased enzyme activity.Overall, these results support the concept that increased hepatic mtGPAT activity associated with obesity positively contributes to lipid disorders by reducing oxidative processes and promoting de novo glycerolipid synthesis. -Lindén, D., L. William-Olsson, M. Rhedin, A-K. Asztély, J. C. Clapham, and S. Schreyer. Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis.

show abstract

The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats

Cited by 18 publications

References 20 publications

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

A Mass Balance Approach to Identify and Compare Differential Routing of¹³C-Labeled Carbohydrates, Lipids, and Proteins In Vivo

Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis

Contact Info

Product

Resources

About

The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats

Cited by 18 publications

References 20 publications

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

Liver Glycogen Reduces Food Intake and Attenuates Obesity in a High-Fat Diet–Fed Mouse Model

A Mass Balance Approach to Identify and Compare Differential Routing of13C-Labeled Carbohydrates, Lipids, and Proteins In Vivo

Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis

Contact Info

Product

Resources

About

A Mass Balance Approach to Identify and Compare Differential Routing of¹³C-Labeled Carbohydrates, Lipids, and Proteins In Vivo