Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 34 APW1.2 | DOI: 10.1530/endoabs.34.APW1.2

University of Cambridge, Cambridge, UK.


The focus of this talk is on how disruptions in the ability of organisms to appropriately store and release lipid can impact on whole organism metabolic health. The talk focuses predominantly on murine phenotyping and discusses how observations from mice can be related to human data.

Both healthy mice and humans preferentially use carbohydrate in the fed state and switch to utilising a greater degree of lipid in fasted state. The ability to perform the switch between utilising carbohydrate and lipid can be defined as ‘metabolic flexibility’. While metabolic flexibility has been extensively studied in humans, data from rodent models with alterations in metabolic flexibility are relatively rare.

The transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is essential for adipogenesis. PPARγ has been implicated in the regulation of both carbohydrate and lipid metabolism and is therefore an excellent candidate for controlling metabolic flexibility. PPARγ2 is the adipose tissue-specific isoform of PPARγ and has greater transcriptional activity than PPARγ1. Despite the known role of PPARγ as a target for the thiazolidinedione class of anti-diabetic drugs, young mice (4 months of age) lacking PPARγ2 had surprisingly normal carbohydrate metabolism based on glucose and insulin tolerance tests.

In this talk, data from mice lacking PPARγ2 will be used to demonstrate how reductions in metabolic flexibility can be detected in mice using indirect calorimetry. The lower metabolic flexibility of the PPARγ2 KO mouse indicated that these animals may have impaired lipid handling, a phenotype which was subsequently confirmed; with PPARγ2 KO mice having reduced rates of lipolysis, and dramatically reduced capacity for whole-organism lipid clearance. Finally, the relationship between reduced adipose tissue capacity for both lipid uptake and release and human metabolic health will be discussed.

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