Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats

Abstract

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.

Hepatic Very Low Density Lipoprotein-ApoB Overproduction Is Associated with Attenuated Hepatic Insulin Signaling and Overexpression of Protein-tyrosine Phosphatase 1B in a Fructose-fed Hamster Model of Insulin Resistance

“…In support of this hypothesis, Yoshino et al (69) showed that in streptozotocintreated, diabetic, hypoinsulinemic rats, fructose feeding increased plasma insulin levels. More recently, Suga et al (70) reported that dietary fructose caused substantial insulin resistance and hyperinsulinemia in both ventromedial hypothalamic-lesioned obese and sham-operated lean rats. Dirlewanger et al (71) also showed that in healthy humans, fructose infusion induced hepatic and extrahepatic insulin resistance.…”

Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats

“…After 14 days of intracerebroventricular injection, animals were fasted 6-7 h before insulin sensitivity was assessed by the SSPG method. This method was originally developed by Reaven and colleagues (43,44) and modified by Suga et al (40). Briefly, rats were anesthetized with pentobarbital (50 mg/kg), and cannulas were implanted in the right jugular vein and carotid artery.…”

Amelioration of Inducible Nitric Oxide Synthase, Insulin like Growth Factor-1 Gene Expression and Insulin Receptor Substrate-1 in Liver Tissue of Insulin Resistant Rats Treated With L-Carnitine

“…Suga et al (2000) suggested that fructose feeding decreases the efficacy of insulin extraction by the liver which retards insulin clearance from the circulation. Hepatic metabolism of fructose leads to alterations in the activities of key enzymes of glucose metabolism Southgate (1995) and activation of stress sensitive pathways that may desensitize insulin signaling Kelley et al (2003).…”