Abstract 20632: Fat Depots From Melanocortin Type 4 Receptor Knock Out and Diet-Induced Obese Mice Contribute Differentially to Cytokine Production During Obese Inflammatory Response

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Introduction: Obesity is an inflammatory disease that increases the risk to develop atrial fibrillation (AF). Although the correlation between increased fat storage and metabolic disease has been established, the identification of the distinct sources from which inflammatory cytokines are being produced is poorly understood.

Hypothesis: We hypothesized that visceral and periatrial fat depots are metabolically more active and contribute differently to the inflammatory response that can increase AF risk and burden in obesity.

Methods: We assessed inflammatory response in 2 independent obese mouse models with increased AF burden: melanocortin type 4 receptor knock out (MC4RKO) and diet-induced obese (DIO) mice. We surgically dissected visceral (gonadal) (VAT), subcutaneous (SAT) and periatrial (PaAT) fat adipose tissue (AT) depots. We purified the RNA and quantified the expression of 3 inflammatory cytokines: IL-6, monocyte chemoattractant protein 1 (MCP1) and TNF-α. All qPCR data are normalized to TATA box-keeping protein gene (TBP), expressed in arbitrary units (au), and presented as mean±SEM. Two-tailed Student’s t-test was used.

Results: IL-6 and MCP1 were upregulated in VAT-MC4RKO (Fig. 1a, p<0.05, n=4 mice/group; 3 and 2-fold increase relative to lean littermates (LEAN) respectively). TNF-α was upregulated in VAT-DIO (Fig. 1a, p<0.0001, n=5 mice/group; 3-fold increase relative to LEAN). MCP1 and TNF-α were also upregulated in SAT-DIO (Fig. 1b, p<0.05, n=5 mice/group; 3-fold increase relative to LEAN). Finally, all 3 cytokines were upregulated in PaAT-DIO (Fig.1c, p<0.05, n=4 mice/group; 3 fold-increase relative to LEAN).

Conclusions: Our data showed that fat depots contribute differentially to cytokine production during obese inflammatory response. VAT is the main fat depot involved in the inflammatory response in MC4RKO mice, whereas all 3 fat depots studied (VAT, SAT and PaAT) are involved in the inflammatory response in DIO mice.

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