Key result
In BATIRKO mice, brown fat lipoatrophy and increased visceral adiposity induced vascular insulin resistance and dysfunction, which was attenuated by anti-TNF-α antibody treatment.
Why the study?
Does anti-TNF-α antibody treatment improve vascular insulin resistance and dysfunction in BATIRKO mice with brown fat lipoatrophy and increased visceral adiposity?
Does anti-TNF-α antibody treatment improve vascular insulin resistance and dysfunction in BATIRKO mice with brown fat lipoatrophy and increased visceral adiposity?
In a mouse model, brown fat lipoatrophy and increased visceral adiposity induce vascular insulin resistance and dysfunction via adipocytokine overexpression, which can be reversed by anti-TNF-α therapy.
Anti-TNF-α may attenuate vascular insulin resistance in this mouse model; leaves open translation to human cardiometabolic disease.
In this study, we analyzed the role played by concerted expression of adipocytokines associated with brown fat lipoatrophy and increased visceral adiposity on triggering vascular insulin resistance and dysfunction in brown adipose tissue (BAT) insulin receptor knockout (BATIRKO) mice. In addition, we assessed whether vascular insulin resistance may aggravate vascular damage. The 52-wk-old, but not 33-wk-old, BATIRKO mice had a significant decrease of BAT mass associated with a significant increase of visceral white adipose tissue (WAT) mass, without changes in body weight. Brown fat lipoatrophy and increased visceral adiposity enhanced the concerted expression of adipocytokines (TNF-α, leptin, and plasminogen activator inhibitor 1) and nuclear factor-κB binding activity in BAT and visceral WAT, mainly in the gonadal depot, and aorta. Although those mice showed insulin sensitivity in the liver and skeletal muscle, insulin signaling in WAT (gonadal depot) and aorta was markedly impaired. Treatment with anti-TNF-α antibody impaired the inflammatory activity in visceral adipose tissue, attenuated insulin resistance in WAT and aorta and induced glucose tolerance. Finally, 52-wk-old BATIRKO mice showed vascular dysfunction, macrophage infiltration, oxidative stress, and a significant increase of gene markers of endothelial activation and inflammation, the latter effect being totally reverted by anti-TNF-α antibody treatment. Our results suggest that brown fat lipoatrophy and increased visceral adiposity through the concerted overexpression of cytoadipokines induces nuclear factor-κB-mediated inflammatory signaling, vascular insulin resistance, and vascular dysfunction. Inhibition of inflammatory activity by anti-TNF-α antibody treatment attenuates vascular insulin resistance and impairs gene expression of vascular dysfunction markers.
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Gómez‐Hernández et al. (2012) studied Vascular insulin resistance and dysfunction. Anti-TNF-α antibody vs. Untreated BATIRKO mice was evaluated on Vascular insulin resistance and dysfunction. In BATIRKO mice, brown fat lipoatrophy and increased visceral adiposity induced vascular insulin resistance and dysfunction, which was attenuated by anti-TNF-α antibody treatment.
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