Abstract
Since chemerin’s identification as an adipokine, it has been associated with a number of human diseases including diabetes and obesity. However, the basic scientific foundation for these clinical determinations is still lacking. Fibroblastic mouse 3T3 cells are unable to develop lipid droplets if chemerin is not present. Thus, we hypothesized that an in vivo rat model chemerin knockout (KO; an advancement from the previously mentioned in vitro cultures) would have limited accumulation of lipid in adipocytes compared to their wild-type (WT) counterparts. Female WT/KO rats (Sprague Dawley background) were fed a low-fat diet starting at 8 weeks of age with weekly body weight and food consumption monitoring. At 25 weeks of age, adipose tissue depots were dissected and flash frozen for PCR analysis or fixed with paraformaldehyde for histology. Over the 17 weeks of experimentation, WT and KO animals did not have differences in total body weight or food consumption but KO animals had a significantly reduced amount of visceral fat compared to WT animals (via microCT at 8 and 25 weeks). Histology of retroperitoneal and mesenteric depots demonstrated a significant leftward shift in adipocyte size in the mesenteric but not the retroperitoneal depot of the KO compared to WT animals. Similarly, in the mesenteric fat of the KO rat, gene expression of adiponectin, fatty acid synthase, perilipin, and leptin were significantly reduced compared to mesenteric fat of WT animals and retroperitoneal fat of both WT and KO animals. Adiponectin was highlighted by a protein-protein interaction network as being important for the physiological effects of chemerin removal. These data are the first, to our knowledge, to demonstrate chemerin’s adipokine potential in vivo and identify it as fat depot location-specific.
Highlights
With the rising obesity crisis around the world, obesity-related diseases such as diabetes [1], non-alcoholic fatty liver disease [2], high blood pressure [3], and even a compound pathology like metabolic syndrome [4] are more frequent
When adipose tissue was fixed, imaged, and analyzed for adipocyte area, the mesenteric adipocytes of the KO animals were significantly smaller than the WT animals
Chemerin may not play a global role in adipogenesis, as evidenced by the lack of changes in the total body weight and retroperitoneal adipocyte size in our chemerin KO rats
Summary
With the rising obesity crisis around the world, obesity-related diseases such as diabetes [1], non-alcoholic fatty liver disease [2], high blood pressure [3], and even a compound pathology like metabolic syndrome [4] are more frequent. Metabolic syndrome is defined as having three of the following five characteristics: high blood pressure, high BMI, dyslipidemia, impaired insulin sensitivity, and a large waist circumference [5]. To better treat patients and predict their prognosis, physicians have looked for blood markers of each of these diseases. Chemerin and adipogenesis and analysis, decision to publish, or preparation of the manuscript
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