Evidence for gender-specific associations between leptin and olfaction.

Abstract The adipocyte-derived hormone leptin regulates food intake by stimulation of the long leptin receptor isoform in the hypothalamus. The long leptin receptor is also expressed in the piriform cortex, an area involved in the relay of olfactory cues. In rodents, both olfaction and leptin influence food seeking. To examine whether serum leptin levels are associated with olfaction in humans. Two distinct samples were analyzed. The population-based sample, 60 men and 61 women, was randomly selected from a population living in Molndal, Sweden. The obese sample, 31 men and 27 women, was from the ongoing Swedish Obese Subjects (SOS) study. Olfactory function was assessed with a two-part test used at Connecticut Chemosensory Clinical Research Center. In the population-based sample, multiple regression analysis revealed a gender difference (interaction gender x leptin; P = .016) between the association of odor identification and logarithmically transformed (log) leptin when adjusting for smoking and log body mass index (BMI). In men the association was positive (beta = 13.2; P = .0026), whereas in women it was negative (beta = -11.4; P = .050). When further adjusting for the influence of menopause and estrogen treatment, the negative association between odor identification and leptin became stronger for women in the population-based sample (beta = -13.7; P = .027). In the obese sample, the associations were similar in direction to those observed in the population-based sample, although nonsignificant. Serum leptin levels were associated with odor identification in a randomly selected population. The association was gender-specific and independent of BMI. High odor identification scores were associated with high serum leptin levels in men and low serum leptin levels in women. This provides further support for previously recognized gender differences in the leptin system and suggests alternative ways for leptin to modulate its effects.