Novel properties of myoferlin in glucose metabolism via pathways involving modulation of adipose functions.

Abstract

While adipose tissue is required to maintain glucose metabolism, excessive calorie intake induces obesity via mechanisms including accelerated proliferation and differentiation of preadipocytes, leading to insulin resistance. Here, we investigated the role of myoferlin (MYOF), a ferlin family protein, in regulating glucose metabolism by mainly focusing on its unknown role in adipose tissue. Whereas young MYOF knockout (KO) mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a high-fat diet (HFD) showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. The Adipose MYOF expression was reduced by aging but was restored by an HFD along with the retained expression of NFAT transcription factors. Loss-of-function of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with the decreased expression of genes involved in adipogenesis. The MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. These insights suggest that the multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories.

• Authors: Yoichi Nozato, Yoichi Takami, Koichi Yamamoto, Motonori Nagasawa, Satoko Nozato, Yuki Imaizumi, Hikari Takeshita, Cheng Wang, Yuki Ito, Shuko Takeda, Yasushi Takeya, Ken Sugimoto, Hironori Nakagami, Rikinari Hanayama, Hiromi Rakugi
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 34 Issue 2 Pg. 2792-2811 (02 2020) ISSN: 1530-6860 [Electronic] United States
• PMID: 31912559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Federation of American Societies for Experimental Biology.

Chemical References

• Membrane Proteins
• Muscle Proteins
• myoferlin protein, mouse
• Glucose

Topics

• Adipocytes (metabolism)
• Adipogenesis (physiology)
• Adipose Tissue, Brown (metabolism)
• Adiposity (physiology)
• Animals
• Cell Differentiation
• Glucose (metabolism)
• Inflammation (metabolism)
• Insulin Resistance (physiology)
• Macrophages (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice, Inbred C57BL
• Muscle Proteins (metabolism)