• Zhu Q, Glazier BJ, Hinkel BC, Cao J, Liu L, Liang C, et al. Neuroendocrine regulation of energy metabolism involving different types of adipose tissues. Int J Mol Sci. 2019;20(11):2707.


    Google Scholar     

  • Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci AMS. 2013;9(2):191–200.


    Google Scholar     

  • Obesity. and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 12 May 2025.

  • Ashraf MJ, Baweja P. Obesity: the ‘Huge’ problem in cardiovascular diseases. Mo Med. 2013;110(6):499–504.


    Google Scholar     

  • Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97.


    Google Scholar     

  • Wang W, Zhu N, Yan T, Shi YN, Chen J, Zhang CJ, et al. The crosstalk: exosomes and lipid metabolism. Cell Commun Signal. 2020;18(1):119.


    Google Scholar     

  • Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88.


    Google Scholar     

  • Neto A, Fernandes A, Barateiro A. The complex relationship between obesity and neurodegenerative diseases: an updated review. Front Cell Neurosci. 2023;17:1294420.


    Google Scholar     

  • Bartness TJ, Ryu V. Neural control of white, beige and brown adipocytes. Int J Obes Suppl. 2015;5(1):S35–9.


    Google Scholar     

  • Wang Y, Leung VH, Zhang Y, Nudell VS, Loud M, Servin-Vences MR, et al. The role of somatosensory innervation of adipose tissues. Nature. 2022;609(7927):569–74.


    Google Scholar     

  • Blaszkiewicz M, Willows JW, Johnson CP, Townsend KL. The importance of peripheral nerves in adipose tissue for the regulation of energy balance. Biology. 2019;8(1):10.


    Google Scholar     

  • Puente-Ruiz SC, Jais A. Reciprocal signaling between adipose tissue depots and the central nervous system. Front Cell Dev Biol. 2022;10:979251.


    Google Scholar     

  • Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol. 2016;231(3):R77–99.


    Google Scholar     

  • Bartness TJ, Liu Y, Shrestha YB, Ryu V. Neural innervation of white adipose tissue and the control of lipolysis. Front Neuroendocrinol. 2014;35(4):473–93.


    Google Scholar     

  • Fan Y, Huang S, Li F, Zhang X, Huang X, Li W, et al. Generation of functional and mature sympathetic neurons from human pluripotent stem cells via a neuroepithelial route. J Mol Neurosci. 2024;74(1):19.


    Google Scholar     

  • Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD, et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med. 2007;13(7):803–11.


    Google Scholar     

  • Szalanczy AM, Key CCC, Woods LCS. Genetic variation in satiety signaling and hypothalamic inflammation: merging fields for the study of obesity. J Nutr Biochem. 2021;101:108928.


    Google Scholar     

  • Xiao Y, Liu D, Cline MA, Gilbert ER. Chronic stress, epigenetics, and adipose tissue metabolism in the obese state. Nutr Metab. 2020;17(1):88.


    Google Scholar     

  • Head GA, Lim K, Barzel B, Burke SL, Davern PJ. Central nervous system dysfunction in obesity-induced hypertension. Curr Hypertens Rep. 2014;16(9):466.


    Google Scholar     

  • do Carmo JM, da Silva AA, Wang Z, Fang T, Aberdein N, de Lara Rodriguez CEP, et al. Obesity-induced hypertension: brain signaling pathways. Curr Hypertens Rep. 2016;18(7):58.


    Google Scholar     

  • Guarino D, Nannipieri M, Iervasi G, Taddei S, Bruno RM. The role of the autonomic nervous system in the pathophysiology of obesity. Front Physiol. 2017;8:665.


    Google Scholar     

  • Chi J, Lin Z, Barr W, Crane A, Zhu XG, Cohen P. Early postnatal interactions between beige adipocytes and sympathetic neurites regulate innervation of subcutaneous fat. eLife. 2021;10:e64693.


    Google Scholar     

  • Huesing C, Qualls-Creekmore E, Lee N, François M, Torres H, Zhang R, et al. Sympathetic innervation of inguinal white adipose tissue in the mouse. J Comp Neurol. 2021;529(7):1465–85.


    Google Scholar     

  • Turtzo LC, Marx R, Lane MD. Cross-talk between sympathetic neurons and adipocytes in coculture. Proc Natl Acad Sci U S A. 2001;98(22):12385–90.


    Google Scholar     

  • Hagberg CE, Spalding KL. White adipocyte dysfunction and obesity-associated pathologies in humans. Nat Rev Mol Cell Biol. 2024;25(4):270–89.


    Google Scholar     

  • Vickers SP, Jackson HC, Cheetham SC. The utility of animal models to evaluate novel anti-obesity agents. Br J Pharmacol. 2011;164(4):1248–62.


    Google Scholar     

  • Börgeson E, Boucher J, Hagberg CE. Of mice and men: pinpointing species differences in adipose tissue biology. Front Cell Dev Biol. 2022;10:1003118.


    Google Scholar     

  • Kyllönen L, Haimi S, Mannerström B, Huhtala H, Rajala KM, Skottman H, et al. Effects of different serum conditions on osteogenic differentiation of human adipose stem cells in vitro. Stem Cell Res Ther. 2013;4(1):17.


    Google Scholar     

  • Ojala M, Prajapati C, Pölönen RP, Rajala K, Pekkanen-Mattila M, Rasku J, et al. Mutation-Specific phenotypes in hiPSC-Derived cardiomyocytes carrying either Myosin-Binding protein C or α-Tropomyosin mutation for hypertrophic cardiomyopathy. Stem Cells Int. 2016;2016(1):1684792.


    Google Scholar     

  • Hongisto H, Ilmarinen T, Vattulainen M, Mikhailova A, Skottman H. Xeno- and feeder-free differentiation of human pluripotent stem cells to two distinct ocular epithelial cell types using simple modifications of one method. Stem Cell Res Ther. 2017;8(1):291.


    Google Scholar     

  • Hyvärinen T, Hyysalo A, Kapucu FE, Aarnos L, Vinogradov A, Eglen SJ, et al. Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures. Sci Rep. 2019;9(1):17125.


    Google Scholar     

  • Kapucu FE, Tujula I, Kulta O, Sukki L, Ryynänen T, Gram H, et al. Human tripartite cortical network model for Temporal assessment of alpha-synuclein aggregation and propagation in parkinson’s disease. Npj Park Dis. 2024;10(1):1–20.


    Google Scholar     

  • Isosaari L, Vuorenpää H, Yrjänäinen A, Kapucu FE, Kelloniemi M, Pakarinen TK, et al. Simultaneous induction of vasculature and neuronal network formation on a chip reveals a dynamic interrelationship between cell types. Cell Commun Signal. 2023;21(1):132.


    Google Scholar     

  • Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82.


    Google Scholar     

  • Rogal J, Binder C, Kromidas E, Roosz J, Probst C, Schneider S, et al. WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications. Sci Rep. 2020;10(1):6666.


    Google Scholar     

  • Pieters VM, Rjaibi ST, Singh K, Li NT, Khan ST, Nunes SS, et al. A three-dimensional human adipocyte model of fatty acid-induced obesity. Biofabrication. 2022;14(4):045009.


    Google Scholar     

  • Schoonjans F, MedCalc. May. MedCalc’s Comparison of proportions calculator. https://www.medcalc.org/calc/comparison_of_proportions.php. Accessed 22 2025.

  • Zhang Y, Chen JW, Chen HY, Wang ZX, Li XD, Xu RX, et al. 3D bioprinted innervation ADMSC self-clustering culture model constructs for in vitro fat metabolism research: a preliminary study of ADMSC and neural progenitor cell co-culture model construct fabrication and characterization. Mater Today Chem. 2022;26:101092.


    Google Scholar     

  • Roxburgh J, Metcalfe AD, Martin YH. The effect of medium selection on adipose-derived stem cell expansion and differentiation: implications for application in regenerative medicine. Cytotechnology. 2016;68(4):957–67.


    Google Scholar     

  • Zebisch K, Voigt V, Wabitsch M, Brandsch M. Protocol for effective differentiation of 3T3-L1 cells to adipocytes. Anal Biochem. 2012;425(1):88–90.


    Google Scholar     

  • Kim JY, Park EJ, Kim SM, Lee HJ. Optimization of adipogenic differentiation conditions for canine adipose-derived stem cells. J Vet Sci. 2021;22(4):e53.


    Google Scholar     

  • Hyväri L, Vanhatupa S, Halonen HT, Kääriäinen M, Miettinen S. Myocardin-related transcription factor A (MRTF-A) regulates the balance between adipogenesis and osteogenesis of human adipose stem cells. Stem Cells Int. 2020;2020(1):8853541.


    Google Scholar     

  • Park A, Kim WK, Bae KH. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells. World J Stem Cells. 2014;6(1):33–42.


    Google Scholar     

  • Liu C, Huang K, Li G, Wang P, Liu C, Guo C, et al. Ascorbic acid promotes 3T3-L1 cells adipogenesis by attenuating ERK signaling to upregulate the collagen VI. Nutr Metab. 2017;14(1):79.


    Google Scholar     

  • Petersen RK, Madsen L, Pedersen LM, Hallenborg P, Hagland H, Viste K, et al. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol Cell Biol. 2008;28(11):3804–16.


    Google Scholar     

  • Wu HF, Saito-Diaz K, Huang CW, McAlpine JL, Seo DE, Magruder DS, et al. Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development. Cell Stem Cell. 2024;31(5):734-753.e8.


    Google Scholar     

  • Rosenberg SS, Spitzer NC. Calcium signaling in neuronal development. Cold Spring Harb Perspect Biol. 2011;3(10):a004259.


    Google Scholar     

  • Turovsky EA, Kaimachnikov NP, Turovskaya MV, Berezhnov AV, Dynnik VV, Zinchenko VP. Two mechanisms of calcium oscillations in adipocytes. Biochem Mosc Suppl Ser Membr Cell Biol. 2012;6(1):26–34.


    Google Scholar     

  • Johnson MA, Weick JP, Pearce RA, Zhang SC. Functional neural development from human embryonic stem cells: accelerated synaptic activity via astrocyte coculture. J Neurosci. 2007;27(12):3069–77.


    Google Scholar     

  • Osaki T, Sivathanu V, Kamm RD. Engineered 3D vascular and neuronal networks in a microfluidic platform. Sci Rep. 2018;8(1):5168.


    Google Scholar     

  • Turovsky EA, Turovskaya MV, Dynnik VV. Deregulation of Ca2+-signaling systems in white adipocytes, manifested as the loss of rhythmic activity, underlies the development of multiple hormonal resistance at obesity and type 2 diabetes. Int J Mol Sci. 2021;22(10):5109.


    Google Scholar     

  • Hatton IA, Galbraith ED, Merleau NSC, Miettinen TP, Smith BM, Shander JA. The human cell count and size distribution. Proc Natl Acad Sci USA. 2023;120(39):e2303077120.


    Google Scholar     

  • Torre EC, Bicer M, Cottrell GS, Widera D, Tamagnini F. Time-dependent reduction of calcium oscillations in adipose-derived stem cells differentiating towards adipogenic and osteogenic lineage. Biomolecules. 2021;11(10):1400.


    Google Scholar     

  • Rathouz MM, Vijayaraghavan S, Berg DK. Acetylcholine differentially affects intracellular calcium via nicotinic and muscarinic receptors on the same population of neurons ∗. J Biol Chem. 1995;270(24):14366–75.


    Google Scholar     

  • Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116–29.


    Google Scholar     

  • Nguyen P, Leray V, Diez M, Serisier S, Bloc’h JL, Siliart B, et al. Liver lipid metabolism. J Anim Physiol Anim Nutr. 2008;92(3):272–83.


    Google Scholar     

  • Louis F, Sowa Y, Kitano S, Matsusaki M. High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ body mass index (BMI). Bioact Mater. 2022;7:227–41.


    Google Scholar     

  • Louis C, Van den Daelen C, Tinant G, Bourez S, Thomé JP, Donnay I, et al. Efficient in vitro adipocyte model of long-term lipolysis: A tool to study the behavior of lipophilic compounds. Vitro Cell Dev Biol – Anim. 2014;50(6):507–18.


    Google Scholar     

  • Halvorsen YD, Bond A, Sen A, Franklin DM, Lea-Currie YR, Sujkowski D, et al. Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis. Metabolism. 2001;50(4):407–13.


    Google Scholar     

  • Lang K, Ratke J. Leptin and adiponectin: new players in the field of tumor cell and leukocyte migration. Cell Commun Signal. 2009;7(1):27.


    Google Scholar     

  • da Silva Rosa SC, Liu M, Sweeney G. Adiponectin synthesis, secretion and extravasation from circulation to interstitial space. Physiology. 2021;36(3):134–49.


    Google Scholar     

  • Shavva VS, Tarnawski L, Liu T, Ahmed O, Olofsson PS. Cholinergic signaling in adipose tissue. Curr Opin Endocr Metab Res. 2024;37:100546.


    Google Scholar     

  • Fadel JR. Regulation of cortical acetylcholine release: insights from in vivo microdialysis studies. Behav Brain Res. 2011;221(2):527–36.


    Google Scholar     

  • El-Habta R, Kingham PJ, Backman LJ. Adipose stem cells enhance myoblast proliferation via acetylcholine and extracellular signal–regulated kinase 1/2 signaling. Muscle Nerve. 2018;57(2):305–11.


    Google Scholar     

  • Parimisetty A, Dorsemans AC, Awada R, Ravanan P, Diotel N, Lefebvre d’Hellencourt C. Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research. J Neuroinflammation. 2016;13:67.


    Google Scholar