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Chapter 10
In a recent study in cell it was found that "increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice."
A. Describe the new lipid structure and compare the structure with other lipids in their family(ies).
B. Describe how the new lipids were identified and characterized.
C. Describe the hypothesized mechanisms of action for the new lipids in their ability to improve lower insulin resistance (i.e. type-2 diabetes).
(B). The targeted mass spectrometry was used for the identification of new lipids and characterized. In mouse tissues, a total of eight PAHSA (Palmitic acid esters of hydroxy–stearic acids) isomers were identified. The isomers are composed of the same acyl chains but differ in the position of the ester bond relative to the carboxyl group.
(C). PAHSA (Palmitic acid esters of hydroxy–stearic acids) levels are reduced in insulin-resistant people, and levels associate highly with insulin sensitivity and PAHSAs have beneficial metabolic effects. Treatment of obese mice with PAHSAs lowers glycemia and develops glucose tolerance while stimulating glucagon-like peptide 1 and insulin secretion.
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