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Abstract
Background
Leptin resistance is a common feature in obese subjects and animals, and this is commonly accompanied with hyperleptinemia. We speculated that one of the causes of leptin resistance is a persistently elevated leptin concentration and then we hypothesized that fluctuations of serum leptin would increase leptin sensitivity in the leptin-resistant state.
Methods
We used a repeated fasting and refeeding (RFR) protocol to produce fluctuation in leptin levels in 7 month-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats, We then measured the leptin sensitivity following an intracerebroventricular (i.c.v.) infusion of leptin.
Results
The OLETF rats exhibited severe visceral fat deposition, hyperleptinemia and leptin resistance. However, in the OLETF-RFR rats, the anorexic effect following i.c.v. leptin infusion was restored. Moreover, the visceral fat mass and serum leptin levels decreased, while the serum adiponectin levels were elevated in the OLETF-RFR rats compared to the OLETF-Control rats. The leptin receptor content in the hypothalamus increased in the OLETF-RFR rats compared to the OLETF-Control rats, and the leptin receptor content in the OLETF-RFR rats decreased compared to that in the the LETO-Control rats.
Figures and Tables
Fig. 1
Effects of intracerebroventricular (i.c.v.) leptin infusion on cumulative food intake in the LETO (A) and OLETF (B) rats. Leptin (15 µg/day) or vehicle (artificial cerebrospinal fluid) was infused for 7 days. Food intake was measured everyday. Values are means ± SE of 5-6 rats per group. P < 0.01 for difference between Vehicle and Leptin by ANOVA with repeated measures in the LETO-Control, -RFR, and -PF rats and OLETF-RFR and -PF rats. The difference between Vehicle and Leptin in each group at the seventh day represented the anorexic effect of i.c.v. infused leptin. RFR, repeated fasting and refeeding; PF, pair fed.
Fig. 2
Effects of intracerebroventricular (i.c.v.) leptin infusion on daily body weight in LETO (A) and OLETF (B) rats. Leptin (15 µg/day) or vehicle (artificial cerebrospinal fluid) was infused for 7 days. Values are means ± SE of 5-6 rats per group. P < 0.01 for difference between Vehicle and Leptin by ANOVA with repeated measures in the LETO-Control, -RFR, and -PF rats and OLETF-RFR rats. RFR, repeated fasting and refeeding; PF, pair fed.
Fig. 3
Leptin receptor (Ob-R) level in the hypothalamus of the experimental groups. Protein level was determined by Western blot. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control. Values are the means ± SE for groups of 5 or 6 rats. * P < 0.05. The Ob-R levels were elevated by RFR and PF compared to Control in OLETF rats (P = 0.004), however, there was no significant difference in LETO rats. Values that do not share a common superscript are significantly different at P < 0.05. RFR, repeated fasting and refeeding; PF, pair fed.
Table 1
Physical and biochemical changes during repeated fasting/refeeding or pair feeding protocol in the experimental groups
Values are means ± S.E.. n.m, not measured. RFR, repeated fasting and refeeding; PF, pair fed. NS, not significant. Initial and final denote the first and 28th day of the experiment. *P < 0.01, vs the corresponding initial. †P < 0.05, ‡P < 0.01, vs the corresponding fed state. a,bThe values of same indication have not significant difference.
Table 2
Effect of intracerebroventricular leptin infusion on serum concentrations of leptin and adiponectin and on visceral fat mass in the experimental groups
Values are means ± S.E.. RFR, repeated fasting and refeeding; PF, pair fed. NS, not significant. Leptin (15 µg/day) or vehicle (artificial cerebrospinal fluid) was infused for 7 days. *P < 0.05, †P < 0.01, vs their vehicle treated rats. ‡P < 0.01, vs the corresponding LETO-Control. a,bThe values of same indication have not significant difference.
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