Inactivation of C/ebp homologous protein-driven immune-metabolic interactions exacerbate obesity and adipose tissue leukocytosis

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)

Successful adaptation to periods of chronic caloric excess is a highly coordinated event that is critical to the survival and propagation of species. Transcription factor C/ebp homologous protein (Chop) is thought to be an important molecular mediator that integrates nutrient signals to endoplasmic reticulum (ER) stress and innate immune activation. Given that aberrant ER stress response is implicated in inducing metabolic inflammation and insulin resistance, we hypothesized that ER stress target gene Chop integrates immune and metabolic systems to adapt to chronic positive energy balance. Here we report that inactivation of Chop in mice fed a high fat diet led to significant increase in obesity caused by a reduction in energy expenditure without any change in food intake. Importantly, ablation of Chop does not induce metabolically healthy obesity, because Chop-deficient mice fed a high fat diet had increased hepatic steatosis with significantly higher insulin resistance. Quantification of adipose tissue leukocytosis revealed that elimination of Chop during obesity led to substantial increase in number of adipose tissue T and B lymphocytes. In addition, deficiency of Chop led to increase in total number of myeloid subpopulations like neutrophils and F4/80(+) adipose tissue macrophages without any alterations in the frequency of M1- or M2-like adipose tissue macrophages. Further

Evidence level

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

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