Obesity is a global epidemic that is causing significant socioeconomic and health problems. An excess of white fat typifies obesity, but newly described beige fat can burn calories through its thermogenic activity, leading to weight loss and metabolic improvements. Identification of the factors regulating beige fat will guide the design of novel therapeutics to treat metabolic disorders.
We aimed to further characterise the lean, obesity-resistant phenotype of the KLF3 knockout (Klf3-/-) mouse model by investigating whether the transcriptional repressor KLF3 plays a role in beige fat formation, i.e. the beiging process. We performed acute cold and thermoneutral temperature experiments with wild-type (WT) and Klf3-/- mice and found that mice lacking KLF3 showed evidence of increased adipose tissue beiging after cold exposure. The increased beiging in Klf3-/- adipose tissue was also observed after thermoneutral housing, albeit to a lesser degree. This implicates KLF3 as a negative regulator of the beiging process.
Gene expression analyses have identified that KLF3 represses key genes in eosinophils, a type of immune cell which has recently been shown to influence adipose tissue metabolism. In the absence of KLF3, a suite of eosinophil genes is de-repressed which may allow eosinophils to secrete more of the factors that promote adipose tissue beiging, which we have termed ‘eosinokines’. We aim to characterise the role of KLF3 in eosinophils in the context of adipose tissue beiging. This work will contribute to a growing understanding of the immune regulation of metabolism in order to help drive the development of targeted weight-loss therapeutics that activate beige fat.