Leptin Modulates Behavioral Responses to Sweet Substances by Influencing Peripheral Taste Structures

Abstract

Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor Ob-Rb. Recently, we proposed that the taste organ is a new peripheral target for leptin. Leptin selectively inhibits mouse taste cell responses to sweet substances and thereby may act as a sweet taste modulator. The present study further investigated leptin action on the taste system by examining expression of Ob-Rb in taste cells and behavioral responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was expressed in taste cells in all strains tested. The db/db mice, however, had a RT-PCR product containing an abnormal db insertion that leads to an impaired shorter intracellular domain. In situ hybridization analysis showed that the hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean and ob/ob mice but not in db/db mice. Two different behavioral tests, one using sweet-bitter mixtures as taste stimuli and the other a conditioned taste aversion paradigm, demonstrated that responses to sucrose and saccharin were significantly decreased after ip injection of leptin in ob/ob and normal littermates, but not in db/db mice. These results suggest that leptin suppresses behavioral responses to sweet substances through its action on Ob-Rb in taste cells. Such taste modulation by leptin may be involved in regulation for food intake.

Taste perception, associated hormonal modulation, and nutrient intake

“…Injection of leptin into lean mice resulted in suppressed response to sweet tastants in peripheral taste nerves without effect on other taste qualities. 80 Shigemura et al 81 demonstrated that the functional leptin receptor Ob-Rb messenger RNA is expressed in the fungiform and circumvallate taste buds in mice and that the presence or absence of Ob-Rb was associated with differences in leptin's effect on behavioral response to sweet substances. Leptin receptor-deficient obese mice showed increased gustatory neural response to sweet compounds.…”

Odour and taste sensitivity is associated with body weight and extent of misreporting of body weight

“…It has been shown by Shigemura et al (2004) that leptin suppresses response to sweet taste stimuli in mice. Leptin is a hormone regulating body weight homeostasis via hypothalamic functional leptin receptor and is elevated in obese compared to lean subjects (Shigemura et al, 2004).…”

“…It has been shown by Shigemura et al (2004) that leptin suppresses response to sweet taste stimuli in mice. Leptin is a hormone regulating body weight homeostasis via hypothalamic functional leptin receptor and is elevated in obese compared to lean subjects (Shigemura et al, 2004). Another study also suggested a negative relationship between pleasantness ratings for sweet stimuli and obesity (Thompson et al, 1976;Kamphuis and Westerterp-Plantenga, 2003).…”

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

“…Transcripts of DC from normal mice displayed a product of correct size (413 bp) for functional Ob-Rb, whereas those from db/db DC showed a larger product (519 bp) due to the gene targeting with an insertion [14][15][16]. The identities of these products were confirmed by sequencing, which showed an abnormal insertion (106 bp) with a stop codon within the coding region for the intracellular domain of Ob-Rb present in db/db DC, as previously reported for other tissues [14][15][16]. Furthermore, flow cytometric analysis confirmed the positive labeling of surface Ob-R on DC from normal control mice (Fig.…”