Uploaded August 2026 | Updated September 2026, 2 weeks ago
The surgery works, the tumor is gone, the hormones are replaced, and the patient gains weight faster than before. This segment explains why: the operation touched the circuit that sets body weight. We walk the POMC brake and the AgRP accelerator, and set the record straight on leptin.
Timestamps:
00:00:00 The name: a tumor built from tooth tissue
00:00:18 Surgery, and what it costs
00:02:11 The new mystery: gaining weight faster than ever
00:08:09 The diagnosis: acquired hypothalamic obesity
00:13:45 How the brain sets weight: the brake and the accelerator
00:16:35 What about leptin?
Resources
Barbell Medicine coaching and templates: barbellmedicine.com
Plus podcast subscription: barbellmedicine.com/shop/subscriptions/plus-podcast-subscription
Barbell Medicine Premium: barbellmedicine.com/shop/subscriptions/barbell-medicine-premium
Signal (book pre-order): barbellmedicine.com/shop/learning/signal
1. Brijmohan A, et al. Acquired hypothalamic obesity following craniopharyngioma resection in a young adult [case report]. 2025. PMCID: PMC12268545; PMID: 40677794.
2. Miller JL, et al; TRANSCEND investigators. Setmelanotide in acquired hypothalamic obesity: a phase 3 randomized trial. N Engl J Med. 2026.
3. Rhythm Pharmaceuticals. FDA approves IMCIVREE (setmelanotide) for acquired hypothalamic obesity. News release. March 19, 2026.
4. US Food and Drug Administration. FDA approves first treatment for weight management for people with certain rare genetic conditions (setmelanotide). 2020.
5. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-908.
6. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879-884.
7. Krude H, Biebermann H, Luck W, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155-157.
8. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095.
9. Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392(6674):398-401.
10. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology. 2010;139(2):448-455.
11. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350(25):2549-2557.
12. Guyenet SJ. The Hungry Brain: Outsmarting the Instincts That Make Us Overeat. Flatiron Books; 2017.
The surgery works, the tumor is gone, the hormones are replaced, and the patient gains weight faster than before. This segment explains why: the operation touched the circuit that sets body weight. We walk the POMC brake and the AgRP accelerator, and set the record straight on leptin.
Timestamps:
00:00:00 The name: a tumor built from tooth tissue
00:00:18 Surgery, and what it costs
00:02:11 The new mystery: gaining weight faster than ever
00:08:09 The diagnosis: acquired hypothalamic obesity
00:13:45 How the brain sets weight: the brake and the accelerator
00:16:35 What about leptin?
Resources
Barbell Medicine coaching and templates: barbellmedicine.com
Plus podcast subscription: barbellmedicine.com/shop/subscriptions/plus-podcast-subscription
Barbell Medicine Premium: barbellmedicine.com/shop/subscriptions/barbell-medicine-premium
Signal (book pre-order): barbellmedicine.com/shop/learning/signal
1. Brijmohan A, et al. Acquired hypothalamic obesity following craniopharyngioma resection in a young adult [case report]. 2025. PMCID: PMC12268545; PMID: 40677794.
2. Miller JL, et al; TRANSCEND investigators. Setmelanotide in acquired hypothalamic obesity: a phase 3 randomized trial. N Engl J Med. 2026.
3. Rhythm Pharmaceuticals. FDA approves IMCIVREE (setmelanotide) for acquired hypothalamic obesity. News release. March 19, 2026.
4. US Food and Drug Administration. FDA approves first treatment for weight management for people with certain rare genetic conditions (setmelanotide). 2020.
5. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-908.
6. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879-884.
7. Krude H, Biebermann H, Luck W, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155-157.
8. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095.
9. Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392(6674):398-401.
10. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology. 2010;139(2):448-455.
11. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350(25):2549-2557.
12. Guyenet SJ. The Hungry Brain: Outsmarting the Instincts That Make Us Overeat. Flatiron Books; 2017.
