8️⃣
Huge thanks to my amazing students Jessie & Charlotte 🙌
and to Stephen X Zhang & @markandermann.bsky.social from @harvardmed.bsky.social & NYU Center for Neural Science for their guidance in analysis, conceptualization, and making sense of it all.

7️⃣
These findings highlight functional alterations in hypothalamic satiety-promoting neurons and reveal the neural consequences of an obesogenic environment.

6️⃣
💡 Interestingly, switching from NCD → HFD didn’t further impair PVH-MC4R neurons, suggesting resilience once these circuits are established.

5️⃣
Importantly, switching obese mice back to a “healthy” diet partially restored feeding behavior, but not neural activity, showing lasting effects of high-fat diet on brain circuits controlling appetite.

4️⃣
🥬 In lean mice, feeding-evoked responses gradually grow as a meal progresses → signals satiety & meal termination.
🍔 In hig- fat-diet-fed mice, responses start too strong and stay flat, suggesting impaired satiety signal integration.

3️⃣
🧩 We found that PVH-MC4R neurons integrate satiety signals during feeding, but this process becomes disrupted in diet induced obesity and can’t be fully rescued by dietary intervention.

2️⃣
These questions drove us to study how these neurons integrate satiety signals (brain “calorie counting”) and drive motivation to eat. 🍽️

🙏 Huge thanks to our fantastic co-authors, especially Charlotte & Jessica, for their incredible help. Grateful to Stephen & @markandermann.bsky.social for their key contributions to experimental design and writing. Thanks to Maria Lehtinen for postdoc guidance and Andermann Lab for their insights.

🧬 Our data suggest that in obesity, feeding responses in PVHMC4R neurons fail to "reset" between meals, possibly due to persistently high leptin and disrupted AgRP/α-MSH signaling.
🎯Future work should assess peptide transmission onto PVHMC4R neurons to pinpoint mechanisms and refine interventions.

🔄 Can switching from a high-fat to a healthy diet reverse brain changes in obesity?

Switching high-fat-diet fed mice to normal chow diet partially restored early-meal PVHMC4R responses and the licking vigor, but the gradual increase in responses was blunted.

⚖️ The strengthened responses were not driven by reduced motivation to consume palatable food - they consumed less despite food restriction and caloric matching to controls.
🧠 This behavioral suppression points to premature satiation rather than motivation deficits.

🍽️ In lean mice, feeding-related responses in PVH-MC4R neurons gradually strengthen during a meal, reflecting growing satiety.
🧠 In mice fed a HFD for many weeks, responses are already strong at meal onset and don’t further increase over the meal, suggesting a disruption in encoding of satiety state.