Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis

Ashley Mulcahy Toney, Rong Fan, Yibo Xian, Virginia Chaidez, Amanda Ramer-Tait, Soonkyu Chung

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)612-620
Number of pages9
JournalObesity
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2019

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Organelle Biogenesis
Insulin Resistance
Macrophages
Adipocytes
Respiration
Triglycerides
Insulin
Ellagic Acid
3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
Liver
Peritoneal Macrophages
High Fat Diet
Glucose Tolerance Test
Dimethyl Sulfoxide
Mitochondrial DNA
Hypertrophy
Energy Metabolism
Adipose Tissue
Obesity
Gene Expression

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis. / Toney, Ashley Mulcahy; Fan, Rong; Xian, Yibo; Chaidez, Virginia; Ramer-Tait, Amanda; Chung, Soonkyu.

In: Obesity, Vol. 27, No. 4, 01.04.2019, p. 612-620.

Research output: Contribution to journalArticle

Toney, Ashley Mulcahy ; Fan, Rong ; Xian, Yibo ; Chaidez, Virginia ; Ramer-Tait, Amanda ; Chung, Soonkyu. / Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis. In: Obesity. 2019 ; Vol. 27, No. 4. pp. 612-620.
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