TY - JOUR
T1 - Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis
AU - Toney, Ashley Mulcahy
AU - Fan, Rong
AU - Xian, Yibo
AU - Chaidez, Virginia
AU - Ramer-Tait, Amanda E.
AU - Chung, Soonkyu
N1 - Funding Information:
agencies: This study is supported by a US Department of Agriculture National Institute of Food and Agriculture Grant awarded to SC and ART (2017-67017-26781). We acknowledge equipment support from the Biomedical and Obesity Core (BORC) at the University of Nebraska-Lincoln. The BORC in the Nebraska Center for Prevention of Obesity Diseases (NPOD) receives partial support from National Institute of General Medical Centers of Biomedical Research Excellence Introducing the Institutional Development (NIGMS COBRE IDeA) award 1P20GM104320.
Funding Information:
Funding agencies: This study is supported by a US Department of Agriculture National Institute of Food and Agriculture Grant awarded to SC and ART (2017-67017-26781). We acknowledge equipment support from the Biomedical and Obesity Core (BORC) at the University of Nebraska-Lincoln. The BORC in the Nebraska Center for Prevention of Obesity Diseases (NPOD) receives partial support from National Institute of General Medical Centers of Biomedical Research Excellence Introducing the Institutional Development (NIGMS COBRE IDeA) award 1P20GM104320. Disclosure: The authors declared no conflict of interest. Additional Supporting Information may be found in the online version of this article. Received: 10 October 2018; Accepted: 8 December 2018; Published online 15 February 2019. doi:10.1002/oby.22404
Publisher Copyright:
© 2019 The Obesity Society
PY - 2019/4
Y1 - 2019/4
N2 - Objective: Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA’s physiological functions related to obesity and insulin resistance remain unclear. Methods: Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high-fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling. The effects of UroA on hepatic triglyceride accumulation, adipocyte size, mitochondrial DNA content, and proinflammatory gene expressions were determined. The impact of UroA on macrophage polarization and mitochondrial respiration were assessed in bone marrow–derived macrophages. Results: Administration of UroA (1) improved systemic insulin sensitivity, (2) attenuated triglyceride accumulation and elevated mitochondrial biogenesis in the liver, (3) reduced adipocyte hypertrophy and macrophage infiltration into the adipose tissue, and (4) altered M1/M2 polarization in peritoneal macrophages. In addition, UroA favored macrophage M2 polarization and mitochondrial respiration in bone marrow-derived macrophages. Conclusions: UroA plays a direct role in improving systemic insulin sensitivity independent of its parental compounds. This work supports UroA’s role in the metabolic benefits of ellagic acid–rich foods and highlights the significance of its microbial transformation in the gut.
AB - Objective: Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA’s physiological functions related to obesity and insulin resistance remain unclear. Methods: Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high-fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling. The effects of UroA on hepatic triglyceride accumulation, adipocyte size, mitochondrial DNA content, and proinflammatory gene expressions were determined. The impact of UroA on macrophage polarization and mitochondrial respiration were assessed in bone marrow–derived macrophages. Results: Administration of UroA (1) improved systemic insulin sensitivity, (2) attenuated triglyceride accumulation and elevated mitochondrial biogenesis in the liver, (3) reduced adipocyte hypertrophy and macrophage infiltration into the adipose tissue, and (4) altered M1/M2 polarization in peritoneal macrophages. In addition, UroA favored macrophage M2 polarization and mitochondrial respiration in bone marrow-derived macrophages. Conclusions: UroA plays a direct role in improving systemic insulin sensitivity independent of its parental compounds. This work supports UroA’s role in the metabolic benefits of ellagic acid–rich foods and highlights the significance of its microbial transformation in the gut.
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U2 - 10.1002/oby.22404
DO - 10.1002/oby.22404
M3 - Article
C2 - 30768775
AN - SCOPUS:85061602074
SN - 1930-7381
VL - 27
SP - 612
EP - 620
JO - Obesity
JF - Obesity
IS - 4
ER -