Worldwide trends in underweight and obesity. from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403(10431):1027–50. https://doi.org/10.1016/s0140-6736(23)02750-2.

Article  Google Scholar 

Global regional. national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. Lancet. 2025;405(10481):813–38. https://doi.org/10.1016/s0140-6736(25)00355-1.

Article  Google Scholar 

Papamargaritis D, le Roux CW, Holst JJ, Davies MJ. New therapies for obesity. Cardiovasc Res. 2024;119(18):2825–42. https://doi.org/10.1093/cvr/cvac176.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Martins C, Roekenes J, Salamati S, Gower BA, Hunter GR. Metabolic adaptation is an illusion, only present when participants are in negative energy balance. Am J Clin Nutr. 2020;112(5):1212–8. https://doi.org/10.1093/ajcn/nqaa220.

Article  PubMed  PubMed Central  Google Scholar 

Flanagan EW, Spann R, Berry SE, Berthoud HR, Broyles S, Foster GD, Krakoff J, Loos RJF, Lowe MR, Ostendorf DM et al. New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium. Obesity (Silver Spring). 2023; 31(12):2895–2908.https://doi.org/10.1002/oby.23905

Elmaleh-Sachs A, Schwartz JL, Bramante CT, Nicklas JM, Gudzune KA, Jay M. Obesity Management in Adults: A Review. JAMA. 2023;330(20):2000–15. https://doi.org/10.1001/jama.2023.19897.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Münzker J, Haase N, Till A, Sucher R, Haange SB, Nemetschke L, Gnad T, Jäger E, Chen J, Riede SJ, et al. Functional changes of the gastric bypass microbiota reactivate thermogenic adipose tissue and systemic glucose control via intestinal FXR-TGR5 crosstalk in diet-induced obesity. Microbiome. 2022;10(1):96. https://doi.org/10.1186/s40168-022-01264-5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Akalestou E, Miras AD, Rutter GA, le Roux CW. Mechanisms of Weight Loss After Obesity Surgery. Endocr Rev. 2022;43(1):19–34. https://doi.org/10.1210/endrev/bnab022.

Article  PubMed  PubMed Central  Google Scholar 

Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514–26. https://doi.org/10.1056/NEJMoa2301972.

Article  PubMed  CAS  Google Scholar 

Smith NK, Grueter BA. Hunger-driven adaptive prioritization of behavior. Febs j. 2022;289(4):922–36. https://doi.org/10.1111/febs.15791.

Article  PubMed  CAS  Google Scholar 

Brüning JC, Fenselau H. Integrative neurocircuits that control metabolism and food intake. Science. 2023;381(6665):eabl7398. https://doi.org/10.1126/science.abl7398.

Article  PubMed  CAS  Google Scholar 

Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J Biol Med. 1951;24(2):123–40.

PubMed  PubMed Central  CAS  Google Scholar 

Zhang J, Chen D, Sweeney P, Yang Y. An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake. Nat Commun. 2020;11(1):6326. https://doi.org/10.1038/s41467-020-20093-4.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Milbank E, Dragano NRV, González-García I, Garcia MR, Rivas-Limeres V, Perdomo L, Hilairet G, Ruiz-Pino F, Mallegol P, Morgan DA, et al. Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation. Nat Metab. 2021;3(10):1415–31. https://doi.org/10.1038/s42255-021-00467-8.

Article  PubMed  CAS  Google Scholar 

Milbank E, Dragano N, Vidal-Gómez X, Rivas-Limeres V, Garrido-Gil P, Wertheimer M, Recoquillon S, Pata MP, Labandeira-Garcia JL, Diéguez C, et al. Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice. Metabolism. 2023;139155350. https://doi.org/10.1016/j.metabol.2022.155350.

Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vázquez MJ, Morgan D, Csikasz RI, Gallego R, Rodriguez-Cuenca S, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012;149(4):871–85. https://doi.org/10.1016/j.cell.2012.02.066.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Martins L, Seoane-Collazo P, Contreras C, González-García I, Martínez-Sánchez N, González F, Zalvide J, Gallego R, Diéguez C, Nogueiras R, et al. A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance. Cell Rep. 2016;16(8):2231–42. https://doi.org/10.1016/j.celrep.2016.07.045.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Martínez de Morentin PB, González-García I, Martins L, Lage R, Fernández-Mallo D, Martínez-Sánchez N, Ruíz-Pino F, Liu J, Morgan DA, Pinilla L, et al. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab. 2014;20(1):41–53. https://doi.org/10.1016/j.cmet.2014.03.031.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Martínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, Buqué X, Aurrekoetxea I, Delgado TC, Vázquez-Martínez R, et al. Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance. Cell Metab. 2017;26(1):212–29. https://doi.org/10.1016/j.cmet.2017.06.014.

Article  PubMed  PubMed Central  CAS  Google Scholar 

López M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010;16(9):1001–8. https://doi.org/10.1038/nm.2207.

Article  PubMed  PubMed Central  CAS  Google Scholar 

González JA, Iordanidou P, Strom M, Adamantidis A, Burdakov D. Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks. Nat Commun. 2016;7:11395. https://doi.org/10.1038/ncomms11395.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Subramanian KS, Lauer LT, Hayes AMR, Décarie-Spain L, McBurnett K, Nourbash AC, Donohue KN, Kao AE, Bashaw AG, Burdakov D, et al. Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats. Nat Commun. 2023;14(1):1755. https://doi.org/10.1038/s41467-023-37344-9.

Article  PubMed  PubMed Central  CAS  Google Scholar 

González JA, Jensen LT, Iordanidou P, Strom M, Fugger L, Burdakov D. Inhibitory Interplay between Orexin Neurons and Eating. Curr Biol. 2016;26(18):2486–91. https://doi.org/10.1016/j.cub.2016.07.013.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Funato H, Tsai AL, Willie JT, Kisanuki Y, Williams SC, Sakurai T, Yanagisawa M. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009;9(1):64–76. https://doi.org/10.1016/j.cmet.2008.10.010.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Tesmer AL, Li X, Bracey E, Schmandt C, Polania R, Peleg-Raibstein D, Burdakov D. Orexin neurons mediate temptation-resistant voluntary exercise. Nat Neurosci. 2024;27(9):1774–82. https://doi.org/10.1038/s41593-024-01696-2.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, Bjorbaek C, Flier JS, Saper CB, Elmquist JK. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron. 1999;23(4):775–86. https://doi.org/10.1016/s0896-6273(01)80035-0.

Article  PubMed  CAS  Google Scholar 

Tan HL, Yin L, Tan Y, Ivanov J, Plucinska K, Ilanges A, Herb BR, Wang P, Kosse C, Cohen P, et al. Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake. Nature. 2024;636(8041):198–205. https://doi.org/10.1038/s41586-024-08108-2.

Article  PubMed  PubMed Central  CAS