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Genetic ablation of C-reactive protein gene confers resistance to obesity and insulin resistance in rats – published online 05/02/2021

Yang graphical abstract

Mengliu Yang, Sheng Qiu, Yirui He, Ling Li, Tong Wu, Ning Ding, Fanghong Li, Allan Z. Zhao, Gangyi Yang

Besides serving as a traditional inflammatory marker in the clinic, C-reactive protein (CRP) is positively associated with the development of obesity, diabetes and cardiovascular diseases. However, genetic evidence is needed to definitively conclude whether CRP directly participates in the regulation of energy and glucose metabolism rather than just being a surrogate marker for these. In this issue, Yang, Qiu et al ( report on a Crp knockout rat model generated to investigate this question. They found that CRP-deficiency led to a significant reduction in weight gain and food intake, elevated energy expenditure and improved insulin sensitivity after exposure to a high-fat diet. Importantly, it also significantly enhanced the weight-reducing effect of leptin. The authors state that this study represents the first line of genetic evidence that CRP is not merely a surrogate blood marker for inflammation and metabolic syndromes, but that it also directly regulates adiposity and insulin sensitivity. They conclude that, clinically, elevated blood CRP levels will negate leptin’s actions. Hence, reduction of CRP-induced leptin resistance may be a promising therapeutic strategy for the treatment of obesity and type 2 diabetes.

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