Hypothalamic Monoaminergic Activity in 11‐Week‐Old Cold‐Exposed Female Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

Abstract

We previously reported that serotonergic activity was reduced in the ventromedial hypothalamic nucleus (VMN) of obese vs. lean male Zucker rats. To verify that this reduction was associated with genotype rather than gender, we measured monoamines and their major metabolites in hypothalamic nuclei of 11-week-old female lean (Fa/Fa) and obese (fa/fa) Zucker rats. In addition, since the thermic response to cold is reported to differ between lean and obese rats, some rats were also exposed to 9 degrees or 22 degrees C for 2h to determine if cold exposure altered hypothalamic monoaminergic activity. As in males, levels of 5-hydroxyindoleacetic acid [5-HIAA; major metabolite of serotonin (5-HT)] and the ratio of 5-HIAA/5-HT were lower in the VMN of obese vs. lean females (P = 0.008, 0.001, respectively). 5-HIAA/5-HT was also reduced in the paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the obese compared to the lean females. Cold exposure significantly stimulated brown fat mitochondrial GDP binding in lean but not obese rats. Similarly, levels of norepinephrine, dopamine (DA), 5-HIAA, and 5-HT in the PVN, and 5-HIAA in the SCN increased in cold-exposed lean but not obese rats. In contrast, VMN and preoptic 3,4-dihydroxyphenylacetic acid (DOPAC; major metabolite of DA) increased in the cold-exposed obese but not lean animals. We conclude that: (1) the blunted peripheral response to cold in obese vs. lean Zucker rats is accompanied by altered hypothalamic monoaminergic activity, the physiological role of which needs further evaluation; and 2) depressed VMN serotonergic activity is associated with the obese genotype (fa/fa) rather than gender and as such may contribute to the reduced sympathetic and enhanced parasympathetic outflow from the VMN.

Adiposity and serum leptin increase in fatty (fa/fa) BNZ neonates without decreased VMH serotonergic activity

“…Because 5-HT 1A receptors in the raphe are inhibitory autoreceptors (7,15), their activation would decrease serotonergic transmission from the raphe. All of these data, as well as the fact that Zucker rats with genetic or diet-induced obesity exhibit lower 5-HT turnover/ release in their VMH than do their lean counterparts (32,33), are consistent with a role for 5-HT in inhibiting food intake and stimulating sympathetic activity.…”

“…5-HT and 5-HIAA were analyzed using HPLC with electrochemical detection as described by Routh et al (33). Peaks were quantified by area and compared with a regression line fitted to a series of standards analyzed throughout the day.…”