Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporation
Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance
Li Cao 0
Xuehui Liu 1
Hongyi Cao 2
Qingguo Lv 1
Nanwei Tong 1
Peter Adhihetty
0 Division of Geriatrics, West China Hospital of Sichuan University , Chengdu 610041 , China
1 Division of Endocrinology and Metabolism, West China Hospital of Sichuan University , Chengdu 610041 , China
2 Division of Endocrinology, The Fifth People's Hospital of Chengdu , Chengdu 611130 , China
Introduction. Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Methods and Results. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferatoractivated receptor-gamma coactivator 1? increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. Conclusion. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.
1. Introduction
There is a special group of individuals who are in
normalweight but have metabolic features observed in overt obesity.
These individuals are not obese on the basis of height
and weight, but are hyperinsulinemic, insulin-resistant, and
predisposed to type 2 diabetes, hypertriglyceridemia, and
premature coronary heart disease. They have been identified
as metabolically obese but normal-weight (MONW)
individuals [
1
]. MONW individuals are very prevalent in the
general population [
2?6
]. Although they have a normal body
mass index or are mildly obese, MONW individuals usually
have obviously increased visceral adipose as measured on
dual X-ray absorptiometry, computed tomography, and
magnetic resonance imaging [
3, 7, 8
]. The increased visceral
fat is strongly associated with insulin resistance and other
metabolic disorders in MONW individuals [
8
].
An animal model of abdominal obesity without
obviously increased body weight would be valuable to study
metabolic disorders mimicking the situations in MONW
individuals. However, almost all available rat models with
metabolic disturbances [
9?11
] are obese models with insulin
resistance.
High-fat and high-sucrose diets are the most frequently
used diets in the establishment of rat models of insulin
resistance. Compared with high-fat diets, high-sucrose diets
do not increase the body weight of rats in the long term [
12?
14
]. Thus, we attempted to develop a rat model of abdominal
obesity with normal weight (AONW) using a modified
high-sucrose diet that provided a smaller proportion of
calories from sucrose than that in general high-sucrose
formulas. The metabolic characteristics, insulin sensitivity,
and morphological changes in liver and muscle were
measured. Gene expressions involved in mitochondrial function
and metabolism of fatty acids and glucose in muscle were
detected in this rat model.
2. Materials and Methods
2.1. Animals and Diets. 4- to 5-week-old male
SpragueDawley rats obtained from the Huaxi Animal Centre of
Sichuan University were randomly assigned to either the
control group (CG) or the HS diet group (HS). The total
calories contained in 100 g of each diet were 349 and 365 kcal
in the CG and HS, respectively. Carbohydrate, protein, and
fats provided 62%, 17%, and 21% of calories, respectively,
in the CG, and 70%, 20%, and 10% of calories, respectively,
in the HS. In the HS diet, sucrose and starch provided 35%
of calories. The chow was offered by the university animal
centre. The amount of daily diet was not limited in either
group. Rats were housed in cages with 12 hours of light
(7:00?19:00), a temperature of 21?C to 26?C, and 60% to
70% humidity. Rats were weighed every 4 days during the
first 4 weeks, then weekly from 5 to 20 weeks.
2.2. Intraperitoneal Glucose Tolerance Test. After 19 weeks of
treatment, rats were fasted for 12 hours before the
intraperitoneal gl (...truncated)