Disease relevance of Dgat1

• We tested whether augmentation of triglyceride synthesis in adipose tissue by transgenic overexpression of the diacylglycerol aclytransferase-1 (Dgat1) gene causes obesity and/or alters insulin sensitivity [1].
• These results suggest that the hyperphagia in Dgat1(-/-) mice is a secondary mechanism that compensates for the increased utilization of fuel substrates [2].
• When fasted in a cold environment, Dgat1(-/-) mice developed hypothermia, which was associated with hypoglycemia [2].

High impact information on Dgat1

• Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat [3].
• Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival [3].
• Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity [3].
• Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females [3].
• Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway [3].

Biological context of Dgat1

• Thus, adipose overexpression of Dgat1 gene in FVB mice leads to diet-inducible insulin resistance, which is secondary to redistribution of fat from adipose tissue to the liver in the absence of obesity [1].
• Adipocytes from Dgat1 transgenic mice displayed increased basal and isoproterenol-stimulated lipolysis rates and decreased gene expression for fatty acid uptake [1].
• Dgat1(-/-) mice had increased energy expenditure irrespective of changes in the ambient temperature [2].
• Dgat1(-/-) mice had increased food intake at baseline, and this hyperphagia became more pronounced upon exposure to cold [2].
• Although core temperature was normal, surface temperature was increased in Dgat1(-/-) mice, most likely reflecting an active mechanism to dissipate heat from increased thermogenesis [2].

Anatomical context of Dgat1

• However, Dgat1(-/-) mice had reduced postabsorptive chylomicronemia (1 h after a high fat challenge) and accumulated neutral-lipid droplets in the cytoplasm of enterocytes when chronically fed a high fat diet [4].
• Adult Dgat(-/-) mice had dry fur and hair loss, which were associated with atrophic sebaceous glands and fur lipid abnormalities [5].

Associations of Dgat1 with chemical compounds

• These results suggest a reduced rate of triacylglycerol absorption in Dgat1(-/-) mice [4].

Other interactions of Dgat1

• Compared with control littermates, Dgat1 transgenic mice were both insulin and leptin resistant and had markedly elevated plasma free fatty acid levels [1].
• Analysis of intestine from Dgat1(-/-) mice revealed activity for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1 [4].

References