Adverse metabolic effects of a hypercaloric, high-fat diet in rodents precede observable changes in body weight.
Although a high-fat diet (HFD) is recognized as an important contributor to obesity, human research is limited by confounders such as income, whereas animal research has typically examined diet during specific developmental periods rather than throughout the lifespan. We hypothesized that the use of an HFD in short-term studies as has been commonly done in animals does not adequately reflect the lifelong dietary patterns seen frequently in humans with consequent metabolic disturbances. We examined the impact of HFD from weaning until 39 weeks (middle age) on the metabolism of male rats. At 7, 26, and 39 weeks, glucose tolerance tests were performed, a subset of animals was euthanized, and serum and tissues were collected. After 4 weeks, preceding increased body weight, HFD animals had increased intra-abdominal fat, triglycerides, and hyperglycemia. Hyperinsulinemia was insufficient to maintain normoglycemia, and beta cell mass and glucagon-like peptide 1 decreased over time in HFD and control animals. Despite lacking significant lipid abnormalities, nonalcoholic fatty liver disease was evident by 39 weeks. Our HFD model demonstrated that significant metabolic abnormalities may go undetected by current standard screening such as weighing and biochemistry.
Division of Maternal-Fetal Medicine, Departments of Obstetrics & Gynecology, Diagnostic Imaging, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada. mcdonals@mcmaster.ca
Sarah D
SD
McDonald
Eric
E
Pesarchuk
Andrew
A
Don-Wauchope
Hala
H
El Zimaity
Alison C
AC
Holloway
D050154:Adiposity; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D038321:Glycemic Index; D006943:Hyperglycemia / Q000209:etiology / Q000503:physiopathology; D006946:Hyperinsulinism / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1