PPAR gamma 2 Prevents Lipotoxicity by Controlling Adipose Tissue Expandability and Peripheral Lipid Metabolism

Abstract

Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted in decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the β-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of β-cells to insulin resistance.

Obesity and related consequences to ageing

“…Since some relatively lean individuals are insulin resistant, whereas some very obese individuals are not, it was proposed that the maximal capacity for AT to expand is an individualize trait, perhaps determined by genetic background (Virtue and Vidal-Puig 2010). Moreover, rodent studies reported that mouse models on the ob/ob background with reduced capacity for ATE (due to partial lack of peroxisome proliferator-activated receptor gamma (PPARγ) function) presented reduced insulin sensitivity in comparison to the very obese ob/ob mice (Virtue and VidalPuig 2010;Medina-Gomez et al 2007). Spalding et al (2008) showed that adipocyte number remains constant in adulthood for both lean and obese individuals, and the difference in cell number between lean and obese is established during childhood and adolescence (Spalding et al 2008).…”

A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction

“…Chow-fed wild-type (WT), obese/obese knockout (ob/ob), Pparg-knockout (PpargKO), and ob/ob/PpargKO (POKO) male mice were generated on a mixed background as previously described [27] and epididymal AT was collected from groups at 4 and 16 weeks of age.…”

Adipose tissue dysregulation and metabolic consequences in childhood and adolescent obesity: potential impact of dietary fat quality

“…It has been demonstrated that knockdown of a key adipogenic gene, PPARγ-2 in the ob/ob mouse model promoted decreased fat mass accompanied by severe IR, β-cell failure and dyslipidaemia compared with control mice (68) . Consistently, ob/ob mice overexpressing adiponectin, i.e.…”