Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression

J Wilsey
2004 Journal of Endocrinology  
The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in dietinduced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344 BN male rats, aged 6 months, were given an i.c.v. injection containing 2 µg leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin
more » ... hicle. Leptin induced a .6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptinstimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptinresistant DIO animals.
doi:10.1677/joe.0.1810297 pmid:15128278 fatcat:lz3p32rqwvefrei5mgazgje3ky