Publication Alert
October 22 2024
This study aimed to investigate the neural mechanisms driving lactational hyperphagia, focusing on the role of hypothalamic AgRP neurons in regulating increased food intake during lactation.
Key Discussion Points:
- Feeding Behavior During Lactation: In this study, the researchers used home cage feeding devices to analyze feeding behavior in mice during mid-late lactation (days 7–17). The data revealed that lactational-hyperphagia is associated with increased meal size, heightened sensitivity to negative energy balance, reduced sensitivity to anorexic stimuli, and an increase in hedonic feeding.
- Role of AgRP Neurons: Hypothalamic neurons expressing agouti-related protein (AgRP), known for their role in homeostatic feeding behavior, were found to be key regulators of lactational-hyperphagia. In vivo imaging and chemogenetics demonstrated that these neurons are highly sensitive to negative energy balance and are directly activated by lactation.
- In Vivo Imaging and Fiber Photometry: The researchers used in vivo fiber photometry and the genetically encoded calcium indicator GCAMP6s to monitor the dynamic activity of AgRP neurons in lactating and non-lactating mice. These neurons exhibited altered activity during lactation, and chemogenetic inhibition of AgRP neurons resulted in a reduction of feeding in lactating mice, highlighting their critical role in driving lactational-hyperphagia.
Plexon products in this study include:
- Multi-Wavelength Fiber Photometry System (MWPHT): The Plexon system was used to record calcium activity in AgRP neurons, enabling real-time analysis of neuronal activity during lactation.
Thoughts for Discussion:
These findings provide new insights into the complex regulation of feeding behavior during lactation and position AgRP neurons as a crucial component in the neural circuitry controlling hyperphagia. The altered in vivo activity of AgRP neurons during lactation suggests that these neurons adapt to the metabolic demands of lactation, potentially serving as targets for interventions aimed at modulating feeding behavior in postpartum mothers.
This study contributes to a growing body of research on the metabolic adaptations during the lactational period and underscores the importance of AgRP neurons in regulating feeding behavior in this context.
Fig. 5 Lactation alters the in vivo activity of AgRP neurons.
A: Schematic outlining fiber photometry recordings of hypothalamic AgRP neurons in awake behaving mice. B: Representative image of GCAMP6s expression in AgRP neurons (green), with the fiber optic trace shown in white. C: Experimental approach for the fast-refeeding (top panels) and palatable food intake (bottom panels) experiments. D and E: Traces of fluorescent signal in the 60 s prior and following the presentation of food before lactation (D) and during lactation in the same mice (E) mice (n = 8 mice for both D and E). F: Change in fluorescence in the 60 s following food introduction before lactation and during lactation. Lactating mice had a significantly greater decreases in calcium activity following food presentation than prior to lactation (n = 8 mice for pre-lactation and lactation groups). G: Change in fluorescence in the 60 s following eating pre-lactation and during lactation in the same mice. Lactating mice had a significantly greater decrease in calcium activity following food consumption than observed prior to lactation (n = 8 mice). H: Average trace of the calcium signal in non-lactating (blue trace) and lactating mice (red trace) aligned to the start of food consumption (time 0 on x-axis). I: Quantification of the change in calcium signal in the 60 s following food consumption in lactating and non-lactating mice. AgRP neurons in lactating mice exhibit a sustained reduction in fluorescence that is not observed in non-lactating animals (n = 8 mice for lactating group and n = 7 mice for non-lactating group). Data represents mean +/− s.e.m. Data points represent individual mice. Data in F, G, and I analyzed with Mann Whitney test. ∗p < 0.05.
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