Transgenic over‐expression of C1q/TNF Related Protein‐1 (CTRP1) in mice increases fatty acid oxidation and reduces adiposity on a high‐fat diet

Abstract

Since the discoveries of leptin, the contribution of adipose tissue as an active endocrine organ has become an essential consideration for the understanding of metabolic diseases. Our laboratory recently discovered a family of novel secreted proteins homologous to adiponectin, designated as C1q/TNF‐related proteins 1‐10 (CTRP1‐10). This study focuses on the metabolic function of CTRP1, a circulating endocrine factor that is produced by adipose tissue. Here we show that circulating levels of CTRP1 are significantly elevated in ob/ob and diet‐induced obese mice relative to lean controls. We generated a transgenic mouse model that over‐expresses CTRP1 (CTRP1‐Tg). When fed a high‐fat diet, we observed a 12 % decrease in body weight gain in CTRP1‐Tg mice relative to control littermates, primarily caused by a reduction in fat mass (−29%), with no significant change in lean body mass. Further, the reduction in adiposity is not due to any changes in food intake or physical activity levels. Instead, this is due to enhanced whole body fatty acid oxidation and energy expenditure based on indirect calorimetry study. Additionally, diet‐induced obese CTRP1‐Tg mice demonstrate increased sensitivity to insulin and increased tolerance to pyruvate relative to control mice. Together, this study provides the first in vivo evidence that CTRP1 is a bona fide adipokine that regulates energy storage and expenditure.