SUMMARY We evaluated factors limiting lactating Mongolian gerbils (Meriones unguiculatus) at three temperatures (10, 21 and 30°C−1 less energy as milk at peak lactation than those allocated to 10 or 21°C, with no difference between the latter groups. On day 14 of lactation, the litter masses at 10 and 30°C were 12.2 and 9.3g lower than those at 21°C, respectively. Lactating gerbils had higher thermal conductance of the fur and lower UCP-1 levels in brown adipose tissue than non-reproductive gerbils, independent of ambient temperature, suggesting that they were attempting to avoid heat stress. Thermal conductance of the fur was positively related to circulating prolactin levels. We implanted non-reproductive gerbils with mini-osmotic pumps that delivered either prolactin or saline. Prolactin did not influence thermal conductance of the fur, but did reduce physical activity and UCP-1 levels in brown adipose tissue. Transferring lactating gerbils from warm to hot conditions resulted in reduced milk production, consistent with the heat dissipation limit theory, but transferring them from warm to cold conditions did not elevate milk production, consistent with the peripheral limitation hypothesis, and placed constraints on pup growth. Supplementary material available online at
Previous studies at 21 °C and 5 °C suggest that in Swiss mice sustained energy intake (SusEI) and reproductive performance are constrained by the mammary capacity to produce milk. We aimed to establish if this constraint also applied at higher ambient temperature (30 °C). Female Swiss mice lactating at 30 °C had lower asymptotic food intake and weaned lighter litters than those at 21 °C. Resting metabolic rate, daily energy expenditure, milk energy output and suckling time were all lower at 30 °C. In a second experiment we gave mice at 30 °C either 6 or 9 pups to raise. Female performance was independent of litter size, indicating that it is probably not controlled by pup demands. In a third experiment we exposed only the mother, or only the offspring to the elevated temperature. In this case the performance of the mother was only reduced when she was exposed, and not when her pups were exposed, showing that the high temperature directly constrains female performance. These data suggest that at 30 °C SusEI and reproductive performance are likely constrained by the capacity of females to dissipate body heat, and not indirectly via pup demands. Constraints seem to change with ambient temperature in this strain of mouse.
Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice. Moreover, the anorectic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b in four different brain regions, we demonstrate that Htr1b engages in spatiotemporally segregated neural pathways to regulate postnatal growth and food intake. Moreover, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the anorexigenic Htr1b circuit, we generated Htr1b-Cre mice. We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single-nucleus RNA sequencing analyses revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons). We show that they regulate food intake, in part, through a Htr1bAgRP→PVH circuit.
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