Evolution of metabolic disorder in rats fed high sucrose or high fat diet: Focus on redox state and mitochondrial function.
Glucotoxicity and lipotoxicity are major hallmarks of metabolic disorder. High consumption of fat or carbohydrate rich food is a major risk of metabolic disorder. However, the evolution of high fat or high carbohydrate diet-induced metabolic disorder is not clear. In the study, we tried to find distinguished and common ways involved in the pathogenesis of insulin resistance induced by high fat (HF) and high sucrose (HS) diet. We found that HS diet induced mild glucose intolerance (2month), followed by a "temporary non-symptom phase" (3month), and then induced significant metabolic abnormality (4month). HF diet induced an early "responsive enhancement phase" (2month), and then gradually caused severe metabolic dysfunction (3-4month). After a mild induction of mitochondrial ROS generation (2month), HS diet resulted in a "temporary non-symptom phase" (3month), and then induced a more significant mitochondrial ROS production (4month). The impairment of mitochondrial function induced by HS diet was progressive (2-4month). HF diet induced gradual mitochondrial ROS generation and hyperpolarization. HF diet induced an early "responsive enhancement" of mitochondrial function (2month), and then gradually resulted in severe decrease of mitochondrial function (3-4month). Despite the patterns of HS and HF diet-induced insulin resistance were differential, final mitochondrial ROS generation combined with mitochondrial dysfunction may be the common pathway. These findings demonstrate a novel understanding of the mechanism of insulin resistance and highlight the pivotal role of mitochondrial ROS generation and mitochondrial dysfunction in the pathogenesis of metabolic disorder.
The First Brigade of Student, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Zi
Z
Long
Department of Research, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Xuesi
X
Zhang
The First Brigade of Student, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Quangui
Q
Sun
Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
Ying
Y
Liu
Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
Nai
N
Liao
Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
Hao
H
Wu
Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: xinwang@fmmu.edu.cn.
Xin
X
Wang
Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: cx-hai@fmmu.edu.cn.
Chunxu
C
Hai
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000009:adverse effects*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008659:Metabolic Diseases; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats
D019422:Dietary Sucrose; D007328:Insulin; D005947:Glucose
High fat diet; High sucrose diet; Metabolic dysfunction; Mitochondrial dysfunction; ROS generation