Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

Author(s)

Pahlavani, Mandana ^{[1, 2]} ; Ramalingam, Latha ^{[1, 2]} ; Miller, Emily K. ^{[1, 2]} ; Scoggin, Shane ^{[1, 2]} ; Menikdiwela, Kalhara R. ^{[1, 2]} ; Kalupahana, Nishan S. ^{[1, 2, 3]} ; Festuccia, William T. ^[4] ; Moustaid-Moussa, Naima ^{[1, 2]}

Affiliation

^[1] Texas Tech Univ, Dept Nutr Sci, Lubbock, TX 79409 - USA

^[2] Texas Tech Univ, Obes Res Cluster, Lubbock, TX 79409 - USA

^[3] Univ Peradeniya, Fac Med, Dept Physiol, Peradeniya 20400 - Sri Lanka

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: MOLECULAR NUTRITION & FOOD RESEARCH; v. 63, n. 7 APR 2019.
• Web of Science Citations: 3

Abstract

Scope Brown adipose tissue (BAT) dissipates energy through uncoupling protein 1 (UCP1) and has been proposed as an anti-obesity target. It was reported previously that a high-fat (HF) diet enriched in eicosapentaenoic acid (EPA) significantly increased UCP1 and other thermogenic markers in BAT. It is hypothesized that these effects are mediated through UCP1-dependent regulation. Methods and results Wild-type (WT) and UCP1 knockout (KO) B6 male mice were housed at thermoneutrality and fed a HF diet, without or with eicosapentaenoic acid (EPA)-enriched fish oil. HF-fed KO mice were heavier and had higher BAT lipid content than other groups. Protective effects of EPA in WT, previously observed at 22 degrees C (reduced adiposity, improved glucose tolerance, and increased UCP1), disappeared at thermoneutrality. Mitochondrial proteins, cytochrome c oxidase subunit 1 (COX I), COX I, II, and IV were reduced in the KO mice compared to WT. Unexpectedly, EPA attenuated weight and fat mass gain and improved glucose tolerance in the KO mice. Finally, EPA increased BAT peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1 alpha) protein and gene expression, and whole-body oxygen consumption in KO mice, consistent with increased mitochondria DNA (mtDNA)/nuclear DNA (nucDNA) ratio. Conclusions EPA rescued the weight gain and glucose intolerance in UCP1 KO mice at thermoneutrality, independent of UCP1; these effects may be mediated in part via increased oxygen consumption and BAT PGC1 alpha. (AU)

• FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants