Physiological role of CD206 macrophages and NAD+ metabolism in obesity and insulin resistance.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20737
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: University of Toyama
• Principal Investigator: Bilal Muhammad 富山大学, 学術研究部医学系, 特命助教 (80968529)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: adipose tissue / M2 macrophages / insulin resistant

Outline of Final Research Achievements

My data showed that transgenic lacking Nampt in M2 macrophages were insulin resistant, with blood glucose levels. Then, I utilized another transgenic mouse lacking M2 receptors that were insulin-sensitive with reduced expression of the inflammatory genes in visceral white adipose tissue. This data further suggests that M2 macrophages are actively involved in regulating glucose metabolism through phenotypic switching. My focus is to investigate the underlying molecular mechanism that regulates these shifting/switching of macrophages, resulting in insulin resistance under high-fat diet-fed conditions. Furthermore, I am generating other M2-related transgenic mice to knock down the M2 signaling conditionally. This will further help me to explore the underlying regulatory mechanism for the treatment of obesity and type 2 diabetes.

Free Research Field

Obesity induced type 2 diabetes

Academic Significance and Societal Importance of the Research Achievements

本研究では、肥満に関連したNAD+の減少とNamptの欠乏が、全身の耐糖能とインスリン感受性を悪化させ、一方で、NAD+の増加が代謝障害を回復させることを示唆している。このメカニズムは、肥満に関連した2型糖尿病の治療に対する新しい戦略を切り開く可能性を持つ。