High-fat- and lipid-induced insulin resistance in rats: the comparison of glucose metabolism, plasma resistin and adiponectin levels.
OBJECTIVE
In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines.


METHODS
In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used.


RESULTS
At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by approximately 25% in the control and approximately 48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 +/- 0.03 to 2.87 +/- 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (G(Rd)) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by approximately 15% compared with the HF and lipid groups where it was suppressed by only approximately 72 and approximately 91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05).


CONCLUSIONS
Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin.
Li
Ling
L
Department of Clinical Biochemistry and Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing University of Medical Sciences, Chongqing, China. lingli31@yahoo.com.cn
Yang
Gangyi
G
Li
Qingming
Q
Tang
Yi
Y
Li
Ke
K
D052242:Adiponectin / Q000032:analysis / Q000097:blood; D000284:Administration, Oral; D000821:Animal Feed / Q000009:adverse effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000139:chemically induced*; D006949:Hyperlipidemias / Q000097:blood* / Q000139:chemically induced; D007262:Infusions, Intravenous; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000032:analysis* / Q000097:blood
D052242:Adiponectin; C499920:Adipoq protein, rat; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D052243:Resistin; C499622:Retn protein, rat; D005947:Glucose