Zhang H, Zhou XD, Shapiro MD, Lip GYH, Tilg H, Valenti L, Somers VK, Byrne CD, Targher G, Yang W, et al. Global burden of metabolic diseases, 1990–2021. Metabolism. 2024;160:155999.
Article CAS PubMed Google Scholar
Chew NWS, Ng CH, Tan DJH, Kong G, Lin C, Chin YH, Lim WH, Huang DQ, Quek J, Fu CE, et al. The global burden of metabolic disease: data from 2000 to 2019. Cell Metab. 2023;35(3):414–28. e413.
Article CAS PubMed Google Scholar
Holm SK, Johansen VBI, Clemmensen C. LEAP2 as a therapeutic target in obesity and cardiometabolic disorders. Rev Endocr Metab Disord 2025.
Garus-Pakowska A. Metabolic Diseases-A challenge for public health in the 21st century. Int J Environ Res Public Health. 2023;20(18):6789.
Article PubMed PubMed Central Google Scholar
Collaboration NCDRF. 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.
Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387(10026):1377–96.
Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat Rev Genet. 2022;23(2):120–33.
Article CAS PubMed Google Scholar
Kusminski CM, Perez-Tilve D, Muller TD, DiMarchi RD, Tschop MH, Scherer PE. Transforming obesity: the advancement of multi-receptor drugs. Cell. 2024;187(15):3829–53.
Article CAS PubMed PubMed Central Google Scholar
Friedman JM. On the causes of obesity and its treatment: the end of the beginning. Cell Metab. 2025;37(3):570–7.
Article CAS PubMed Google Scholar
Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L, Mantzoros CS. Emerging pharmacotherapies for obesity: A systematic review. Pharmacol Rev. 2025;77(1):100002.
Muller TD. Advances in incretin-based drug discovery in 2025. Nat Rev Endocrinol. 2025;22(2):68–9.
Dragano NRV, Ferno J, Dieguez C, Lopez M, Milbank E. Recent updates on obesity treatments: available drugs and future directions. Neuroscience. 2020;437:215–39.
Article CAS PubMed Google Scholar
Argente J, Farooqi IS, Chowen JA, Kuhnen P, Lopez M, Morselli E, Gan HW, Spoudeas HA, Wabitsch M, Tena-Sempere M. Hypothalamic obesity: from basic mechanisms to clinical perspectives. Lancet Diabetes Endocrinol. 2025;13(1):57–68.
Article CAS PubMed Google Scholar
Clemmensen C, Finan B, Muller TD, DiMarchi RD, Tschop MH, Hofmann SM. Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases. Nat Rev Endocrinol. 2019;15(2):90–104.
Muller TD, Bluher M, Tschop MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022;21(3):201–23.
Bruning JC, Fenselau H. Integrative neurocircuits that control metabolism and food intake. Science. 2023;381(6665):eabl7398.
Lee TH, Nicolas JC, Quarta C. Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins. J Endocrinol Invest. 2024;47(11):2627–48.
Article CAS PubMed Google Scholar
Schneeberger M, Gomis R, Claret M. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J Endocrinol. 2014;220(2):T25–46.
Article CAS PubMed Google Scholar
Lopez M, Nogueiras R, Tena-Sempere M, Dieguez C. Hypothalamic AMPK: a canonical regulator of whole-body energy balance. Nat Rev Endocrinol. 2016;12(7):421–32.
Article CAS PubMed Google Scholar
Lopez M. Hypothalamic AMPK as a possible target for energy balance-related diseases. Trends Pharmacol Sci. 2022;43(7):546–56.
Article CAS PubMed Google Scholar
Le Thuc O, Garcia-Caceres C. Obesity-induced inflammation: connecting the periphery to the brain. Nat Metab. 2024;6(7):1237–52.
Lopez M, Tena-Sempere M, Dieguez C. Cross-talk between orexins (hypocretins) and the neuroendocrine axes (hypothalamic-pituitary axes). Front Neuroendocrinol. 2010;31(2):113–27.
Article CAS PubMed Google Scholar
Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021;20(5):362–83.
Article CAS PubMed Google Scholar
Wu D, Chen Q, Chen X, Han F, Chen Z, Wang Y. The blood-brain barrier: structure, regulation, and drug delivery. Signal Transduct Target Ther. 2023;8(1):217.
Article PubMed PubMed Central Google Scholar
Saraiva C, Praca C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release. 2016;235:34–47.
Article CAS PubMed Google Scholar
Nampoothiri S, Nogueiras R, Schwaninger M, Prevot V. Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis. Nat Metab. 2022;4(7):813–25.
Article PubMed PubMed Central Google Scholar
Chen B, de Launoit E, Meseguer D, Garcia Caceres C, Eichmann A, Renier N, Schneeberger M. The interactions between energy homeostasis and neurovascular plasticity. Nat Rev Endocrinol. 2024;20(12):749–59.
Garcia-Caceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, et al. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nat Neurosci. 2019;22(1):7–14.
Article CAS PubMed Google Scholar
Korbelin J, Arrulo A, Schwaninger M. Gene therapy targeting the blood-brain barrier. Vitam Horm. 2024;126:191–217.
Chen B, Furtado J, Schneeberger M. Neurovascular plasticity as a modulator of hypothalamic function. Rev Endocr Metab Disord. 2025.
Steuernagel L, Lam BYH, Klemm P, Dowsett GKC, Bauder CA, Tadross JA, Hitschfeld TS, Del Rio Martin A, Chen W, de Solis AJ, et al. HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus. Nat Metab. 2022;4(10):1402–19.
Article CAS PubMed PubMed Central Google Scholar
Tadross JA, Steuernagel L, Dowsett GKC, Kentistou KA, Lundh S, Porniece M, Klemm P, Rainbow K, Hvid H, Kania K, et al. A comprehensive spatio-cellular map of the human hypothalamus. Nature. 2025;639(8055):708–16.
Article CAS PubMed PubMed Central Google Scholar
Mukherjee S, Skrede S, Ferno J. The hypothalamus as a therapeutic target: towards novel approaches for managing antipsychotic-induced weight gain. Rev Endocr Metab Disord. 2025.
Campbell JN, Macosko EZ, Fenselau H, Pers TH, Lyubetskaya A, Tenen D, Goldman M, Verstegen AM, Resch JM, McCarroll SA, et al. A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci. 2017;20(3):484–96.
Article CAS PubMed PubMed Central Google Scholar
Nance E. Brain-Penetrating nanoparticles for analysis of the brain microenvironment. Methods Mol Biol. 2017;1570:91–104.
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