C Brent Wakefield1,2, Vanessa R Lee1, Danielle Johnston1, Parastoo Boroumand3,4, Nicolas J Pillon3,5, Samar Sayedyahossein1,6, Brooke L O'Donnell1, Justin Tang1, Rafael E Sanchez-Pupo1, Kevin J Barr1, Robert Gros6,7, Lauren Flynn1,2,8, Nica M Borradaile6, Amira Klip3,5, Frank Beier2,6, Silvia Penuela9,10,11. 1. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada. 2. Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, ON, N6G 2V4, Canada. 3. Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. 4. Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada. 5. Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. 6. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, N6A 5C1, Canada. 7. Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada. 8. Department of Chemical and Biomedical Engineering, University of Western Ontario, London, ON, N6A 5C1, Canada. 9. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada. spenuela@uwo.ca. 10. Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for Musculoskeletal Research, University Hospital, London, ON, N6G 2V4, Canada. spenuela@uwo.ca. 11. Department of Oncology, Division of Experimental Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada. spenuela@uwo.ca.
Abstract
BACKGROUND: Pannexin 3 (PANX3) is a channel-forming glycoprotein that enables nutrient-induced inflammation in vitro, and genetic linkage data suggest that it regulates body mass index. Here, we characterized inflammatory and metabolic parameters in global Panx3 knockout (KO) mice in the context of forced treadmill running (FEX) and high-fat diet (HFD). METHODS: C57BL/6N (WT) and KO mice were randomized to either a FEX running protocol or no running (SED) from 24 until 30 weeks of age. Body weight was measured biweekly, and body composition was measured at 24 and 30 weeks of age. Male WT and KO mice were fed a HFD from 12 to 28 weeks of age. Metabolic organs were analyzed for a panel of inflammatory markers and PANX3 expression. RESULTS: In females there were no significant differences in body composition between genotypes, which could be due to the lack of PANX3 expression in female white adipose tissue, while male KOs fed a chow diet had lower body weight and lower fat mass at 24 and 30 weeks of age, which was reduced to the same extent as 6 weeks of FEX in WT mice. In addition, male KO mice exhibited significantly lower expression of multiple pro-inflammatory genes in white adipose tissue compared to WT mice. While on a HFD body weight differences were insignificant, multiple inflammatory genes were significantly different in quadriceps muscle and white adipose tissue resulting in a more anti-inflammatory phenotype in KO mice compared to WT. The lower fat mass in male KO mice may be due to significantly fewer adipocytes in their subcutaneous fat compared to WT mice. Mechanistically, adipose stromal cells (ASCs) cultured from KO mice grow significantly slower than WT ASCs. CONCLUSION: PANX3 is expressed in male adult mouse adipose tissue and may regulate adipocyte numbers, influencing fat accumulation and inflammation.
BACKGROUND: Pannexin 3 (PANX3) is a channel-forming glycoprotein that enables nutrient-induced inflammation in vitro, and genetic linkage data suggest that it regulates body mass index. Here, we characterized inflammatory and metabolic parameters in global Panx3 knockout (KO) mice in the context of forced treadmill running (FEX) and high-fat diet (HFD). METHODS: C57BL/6N (WT) and KO mice were randomized to either a FEX running protocol or no running (SED) from 24 until 30 weeks of age. Body weight was measured biweekly, and body composition was measured at 24 and 30 weeks of age. Male WT and KO mice were fed a HFD from 12 to 28 weeks of age. Metabolic organs were analyzed for a panel of inflammatory markers and PANX3 expression. RESULTS: In females there were no significant differences in body composition between genotypes, which could be due to the lack of PANX3 expression in female white adipose tissue, while male KOs fed a chow diet had lower body weight and lower fat mass at 24 and 30 weeks of age, which was reduced to the same extent as 6 weeks of FEX in WT mice. In addition, male KO mice exhibited significantly lower expression of multiple pro-inflammatory genes in white adipose tissue compared to WT mice. While on a HFD body weight differences were insignificant, multiple inflammatory genes were significantly different in quadriceps muscle and white adipose tissue resulting in a more anti-inflammatory phenotype in KO mice compared to WT. The lower fat mass in male KO mice may be due to significantly fewer adipocytes in their subcutaneous fat compared to WT mice. Mechanistically, adipose stromal cells (ASCs) cultured from KO mice grow significantly slower than WT ASCs. CONCLUSION: PANX3 is expressed in male adult mouse adipose tissue and may regulate adipocyte numbers, influencing fat accumulation and inflammation.
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