Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet.

Abstract

It has been shown that adipose tissue hyperplasia (increased adipocyte number or adipogenesis) has beneficial effects on metabolic health. The aim of the present study was to determine whether phytol could modulate hyperplasia/adipogenesis and glucose homeostasis, and to explore the underlying mechanisms in mice fed high-fat and high fructose diet (HFFD). Our results demonstrated that phytol administration decreased body weight gain and inguinal subcutaneous white adipose tissue (iWAT) weight. However, phytol significantly increased the adipocyte number in iWAT, with the smaller average adipocyte diameter. Meanwhile, OGTT result showed that phytol improved glucose tolerance. In accord, phytol administration markedly increased expression of marker genes associated with adipogenesis (PPARγ and C/EBPα) and glucose uptake (AS160 and GLUT4) and activated PI3K/Akt signaling pathway in mice iWAT. In agreement with the in vivo findings, the in vitro results indicated that 100 μM phytol significantly enhanced 3T3-L1 adipogenesis and glucose uptake, and activated PI3K/Akt signaling pathway. However, phytol-induced enhancement of 3T3-L1 adipognesis and glucose uptake, activation of PI3K/Akt signaling pathway, elevation of marker genes involved in adipogensis and glucose uptake, as well as translocation of GLUT4 from cytoplasm to membrane were abolished by Wortmannin, a specific PI3K/Akt inhibitor. Taken together, phytol increased adipocyte number in iWAT and improved glucose tolerance in mice fed HFFD, which was coincident with the enhanced adipogenesis and glucose uptake in 3T3-L1, and was associated with activation of PI3K/Akt signaling pathway. These data suggested the application of phytol as a potential nutritional agent to combat obesity and type 2 diabetes.

• Authors: Jianbing Wang, Xiaoquan Hu, Wei Ai, Fenglin Zhang, Kelin Yang, Lina Wang, Xiaotong Zhu, Ping Gao, Gang Shu, Qingyan Jiang, Songbo Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 489 Issue 4 Pg. 432-438 (08 05 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 28571740 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Androstadienes
• Phosphoinositide-3 Kinase Inhibitors
• Phytol
• Fructose
• Proto-Oncogene Proteins c-akt
• Wortmannin

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects)
• Androstadienes (pharmacology)
• Animals
• Cell Count
• Cell Differentiation (drug effects)
• Cells, Cultured
• Diabetes Mellitus, Experimental
• Diet, Carbohydrate Loading (adverse effects)
• Diet, High-Fat (adverse effects)
• Fructose (administration & dosage, adverse effects)
• Glucose Tolerance Test
• Mice
• Mice, Inbred C57BL
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phytol (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Wortmannin