Effects of different free fatty acids on insulin resistance in rats.
BACKGROUND
Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance.


METHODS
Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method.


RESULTS
Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (P<0.001). All three fat infusions caused remarkably higher hepatic glucose production (HGP) than SAL (P<0.001). OLE and LOH infusions induced much higher HGP than IH (P<0.01). Glucose utilization (GU) was decreased with all three fat infusions relative to SAL (P<0.001), but GU did not differ among the three types of fat infusions.


CONCLUSIONS
Short-term elevation of FFAs can induce hepatic and peripheral insulin resistance. Polyunsaturated fatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.
Han
Ping
P
Department of Endocrinology, Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China. hanping85@hotmail.com
Zhang
Yong-Yan
YY
Lu
Yan
Y
He
Bing
B
Zhang
Wei
W
Xia
Fei
F
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D015309:Glucose Clamp Technique; D006493:Heparin / Q000494:pharmacology; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D001786:Blood Glucose; D002096:C-Peptide; D004041:Dietary Fats; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D019301:Oleic Acid; D006493:Heparin; C029310:lard