Aconitate decarboxylase 1 regulates glucose homeostasis and obesity in mice

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective The intersection between immunology and metabolism contributes to the pathogenesis of obesity-associated metabolic diseases as well as molecular control of inflammatory responses. The metabolite itaconate and the cell-permeable derivatives have robust anti-inflammatory effects; therefore, it is hypothesized that cis-aconitate decarboxylase (Acod1)-produced itaconate has a protective, anti-inflammatory effect during diet-induced obesity and metabolic disease. Methods Wild-type and Acod1 -/- mice were subjected to diet-induced obesity. Glucose metabolism was analyzed by glucose tolerance tests, insulin tolerance tests, and indirect calorimetry. Gene expression and transcriptome analysis was performed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and RNA sequencing. Results Wild-type and Acod1 -/- mice on high-fat diet had equivalent weight gain, but Acod1 -/- mice had impaired glucose metabolism. Insulin tolerance tests and glucose tolerance tests after 12 weeks on high-fat diet revealed significantly higher blood glucose levels in Acod1 -/- mice. This was associated with significant enrichment of inflammatory gene sets and a reduction in genes related to adipogenesis and fatty acid metabolism. Analysis of naive Acod1 -/- mice showed a significant increase in fat deposition at 3 and 6 months of age and obesity and insulin resistance by 12

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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