J Korean Endocr Soc.  2008 Oct;23(5):310-318. 10.3803/jkes.2008.23.5.310.

The Effect of Leptin Level Fluctuations by a Repeated Fasting/Refeeding on the Leptin Sensitivity in OLETF Rats

Affiliations
  • 1Department of OBGY, College of Medicine, Yeungnam University, Korea.
  • 2Department of Pediatrics, College of Medicine, Yeungnam University, Korea.
  • 3Department of Physiology, College of Medicine, Yeungnam University, Korea.
  • 4Department of Internal Medicine, College of Medicine, Yeungnam University, Korea.

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.
CONCLUSION
These results suggest that the intermittent suppression of the serum leptin level reversed the leptin resistance in OLEFT rats, and this may have occurred due to an increased number of leptin receptors in the hypothalamus.

Keyword

fasting/refeeding; food intake; leptin resistance; OLETF rats

MeSH Terms

Adiponectin
Animals
Diethylpropion
Eating
Fasting
Hypothalamus
Intra-Abdominal Fat
Leptin
Rats
Rats, Inbred OLETF
Receptors, Leptin
Adiponectin
Diethylpropion
Leptin
Receptors, Leptin

Figure

  • 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.


Cited by  1 articles

The Effect of Food Restriction on Appetite Regulating Hormones and Adiponectin Activity
Ki Hoon Kim, Hyun Kook Kim
Korean J Nutr. 2012;45(1):5-11.    doi: 10.4163/kjn.2012.45.1.5.


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