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Obesity's cognitive consequences: leptin's influence on dementia

Year 2024, Volume: 7 Issue: 3, 346 - 351, 27.05.2024
https://doi.org/10.32322/jhsm.1462938

Abstract

Dementia is characterised by progressive cognitive decline and is increasingly associated with obesity. Obesity is characterised by a number of pathological features, including excess fat accumulation, insulin resistance, gut dysbiosis, oxidative stress, inflammatory activation and systemic inflammation. These pathological factors trigger neuroinflammation and brain damage, highlighting the complex relationship between metabolic health and cognitive function. The amount of leptin in the bloodstream correlates with the amount of body fat and regulates cognitive processes as well as metabolic functions through its effects on the central nervous system. However, obesity can lead to leptin resistance, which may contribute to the development of neurodegenerative disorders such as dementia by impairing leptin's ability to maintain cognitive function. This article discusses the gut-brain axis as a critical mediator of the effects of obesity on cognitive health and highlights the impact of gut dysbiosis on cognitive decline as a result of neuroinflammation. Obesity-specific systemic inflammation exacerbates neurodegeneration, highlighting the need for integrated approaches to treat obesity and its cognitive consequences. Addressing the pathological features of obesity by optimising leptin signalling may offer promising strategies to prevent or slow the progression of cognitive decline associated with obesity and metabolic syndrome.

References

  • GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7(2):e105-e125. doi: 10.1016/S2468-2667(21)00249-8
  • World Health Organization. Obesity and overweight. Updated 2021. Accessed July 28, 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  • Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017;13(4):851-863. doi:10.5114/aoms.2016.58928
  • Moser VA, Christensen A, Liu J, et al. Effects of aging, high-fat diet, and testosterone treatment on neural and metabolic outcomes in male brown Norway rats. Neurobiol Aging. 2019; 73:145-160. doi: 10.1016/j.neurobiolaging.2018.09.016
  • Loffredo L, Ettorre E, Zicari AM, et al. Oxidative stress and gut-derived lipopolysaccharides in neurodegenerative disease: role of NOX2. Oxid Med Cell Longev. 2020;2020:8630275. doi: 10.1155/2020/8630275
  • Forsythe P, Bienenstock J, Kunze WA. Vagal pathways for microbiome-brain-gut axis communication. Adv Exp Med Biol. 2014;817:115-133. doi: 10.1007/978-1-4939-0897-4_5
  • Isidori AM, Strollo F, Morè M, et al. Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab. 2000;85(5):1954-1962.
  • van Andel M, van Schoor NM, Korten NC, Comijs HC, Heijboer AC, Drent ML. The association between high-molecular-weight adiponectin, ghrelin and leptin and age-related cognitive decline: results from longitudinal aging study Amsterdam. J Gerontol A Biol Sci Med Sci. 2021;76(1):131-140.
  • Nguyen TT, Ta QTH, Nguyen TKO, Nguyen TTD, Van Giau V. Type 3 diabetes and its role implications in Alzheimer’s disease. Int J Mol Sci. 2020;21(9):3165. doi: 10.3390/ijms21093165
  • Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer’s disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1078-1089. doi: 10.1016/j.bbadis.2016. 08.018
  • Selman A, Burns S, Reddy AP, Culberson J, Reddy PH. The role of obesity and diabetes in dementia. Int J Mol Sci. 2022;23(16):9267. doi: 10.3390/ijms23169267
  • Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-1143.
  • Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-867.
  • Bowman K, Thambisetty M, Kuchel GA, Ferrucci L, Melzer D. Obesity and longer term risks of dementia in 65–74 year olds. Age Ageing. 2019;48(3):367-373. doi: 10.1093/ageing/afz020
  • Joo SH, Yun SH, Kang DW, Hahn CT, Lim HK, Lee CU. Body mass index in mild cognitive impairment according to age, sex, cognitive intervention, and hypertension and risk of progression to Alzheimer’s disease. Front Psychiatry. 2018;9:142. doi: 10.3389/fpsyt.2018.00142
  • Wu H, Ghosh S, Perrard XD, et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 2007; 115(8):1029-1038.
  • Kiliaan AJ, Arnoldussen IA, Gustafson DR. Adipokines: a link between obesity and dementia? Lancet Neurol. 2014;13(9):913-923.
  • Emmerzaal TL, Kiliaan AJ, Gustafson DR. 2003-2013: a decade of body mass index, Alzheimer’s disease, and dementia. J Alzheimers Dis. 2015;43(3):739-755.
  • García-Ptacek S, Faxén-Irving G, Čermáková P, Eriksdotter M, Religa D. Body mass index in dementia. Eur J Clin Nutr. 2014; 68(11):1204-1209.
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  • Procaccini C, Santopaolo M, Faicchia D, et al. Role of metabolism in neurodegenerative disorders. Metabolism. 2016;65(9):1376-1390.
  • Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am J Clin Nutr. 2005;81(6):1335-1341.
  • Beyer F, Kharabian Masouleh S, Kratzsch J, et al. A metabolic obesity profile is associated with decreased gray matter volume in cognitively healthy older adults. Front Aging Neurosci. 2019; 11:202.
  • Hou Q, Guan Y, Yu W, et al. Associations between obesity and cognitive impairment in the Chinese elderly: an observational study. Clin Interv Aging. 2019;14:367-373.
  • Pannacciulli N, Del Parigi A, Chen K, Le DSN, Reiman EM, Tataranni PA. Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage. 2006;31(4):1419-1425.
  • Gunstad J, Paul RH, Cohen RA, Tate DF, Spitznagel MB, Gordon E. Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry. 2007;48(1):57-61.
  • Raji CA, Ho AJ, Parikshak NN, et al. Brain structure and obesity. Hum Brain Mapp. 2010;31(3):353-364.
  • Marqués-Iturria I, Pueyo R, Garolera M, et al. Frontal cortical thinning and subcortical volume reductions in early adulthood obesity. Psychiatry Res Neuroimaging. 2013;214(2):109-115.
  • Yokum S, Ng J, Stice E. Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes. 2012;36(5):656-664.
  • Debette S, Wolf C, Lambert JC, et al. Abdominal obesity and lower gray matter volume: a Mendelian randomization study. Neurobiol Aging. 2014;35(2):378-386.
  • Veit R, Kullmann S, Heni M, et al. Reduced cortical thickness associated with visceral fat and BMI. NeuroImage Clin. 2014; 6:307-311.
  • Pistell PJ, Morrison CD, Gupta S, et al. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol. 2010;219(1-2):25-32.
  • Winocur G, Greenwood CE. Studies of the effects of high fat diets on cognitive function in a rat model. Neurobiol Aging. 2005;26(1):46-49.
  • Wong Zhang DE, Tran V, Vinh A, et al. Pathophysiological links between obesity and dementia. Neuromolecular Med. 2023; 25(4):451-456.
  • Kothari V, Luo Y, Tornabene T, et al. High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochim Biophys Acta Mol Basis Dis. 2017;1863(2):499-508.
  • Saiyasit N, Chunchai T, Prus D, et al. Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet-induced obese condition. Nutrition. 2020;69:110576.
  • Hajiluian G, Abbasalizad Farhangi M, Nameni G, Shahabi P, Megari-Abbasi M. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats. Nutr Neurosci. 2018;21(10):744-752.
  • Guo DH, Yamamoto M, Hernandez CM, Khodadadi H, Baban B, Stranahan AM. Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells. J Clin Invest. 2020;130(4):1961-1976.
  • Erichsen JM, Fadel JR, Reagan LP. Peripheral versus central insulin and leptin resistance: role in metabolic disorders, cognition, and neuropsychiatric diseases. Neuropharmacol. 2022;203:108877.
  • Tian J, Wang T, Jia K, Guo L, Swerdlow RH, Du H. Nonobese male patients with Alzheimer’s disease are vulnerable to decrease in plasma leptin. J Alzheimers Dis. 2022;88(3):1017-1027.
  • Wang R, Yu C, Tang Z, et al. Leptin induces altered differentiation of keratinocytes by inducing insulin resistance: implications for metabolic syndrome-induced resistance of psoriatic therapy. J Dermatolog Treat. 2024;35(1):2309305.
  • Turner A, Hoyos C, Mowszowski L, et al. Obesity and oxidative stress in older adults at risk for dementia: a magnetic resonance spectroscopy study. Alzheimer Dis Assoc Disord. 2021;35(2):121-127.
  • Vamanu E, Rai SN. The link between obesity, microbiota dysbiosis, and neurodegenerative pathogenesis. Diseases. 2021;9(3):45.
  • Wieczorek M, Swiergiel AH, Pournajafi-Nazarloo H, Dunn AJ. Physiological and behavioral responses to interleukin-1β and LPS in vagotomized mice. Physiol Behav. 2005;85(4):500-511.
  • Casado ME, Collado-Pérez R, Frago LM, Barrios V. Recent advances in the knowledge of the mechanisms of leptin physiology and actions in neurological and metabolic pathologies. Int J Mol Sci. 2023;24(2):1422.
  • Lindhorst A, Raulien N, Wieghofer P, et al. Adipocyte death triggers a pro-inflammatory response and induces metabolic activation of resident macrophages. Cell Death Dis. 2021; 12(6):579.
  • Wu D, Molofsky AB, Liang HE, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332(6026):243-247.
  • Frühbeck G. Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol Biol. 2008;456:1-22.
  • Fietta P, Delsante G. Focus on adipokines. Theor Biol Forum. 2013;106(1-2):103-129.
  • Paul RF, Hassan M, Nazar HS, Gillani S, Afzal N, Qayyum I. Effect of body mass index on serum leptin levels. J Ayub Med Coll Abbottabad. 2011;23(3):40-43.
  • Kennedy A, Gettys TW, Watson P, et al. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab. 1997;82(4):1293-1300.
  • Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest. 1996;97(5):1344-1347.
  • Wada N, Hirako S, Takenoya F, Kageyama H, Okabe M, Shioda S. Leptin and its receptors. J Chem Neuroanat. 2014;61:191-199.
  • Hsuchou H, Kastin AJ, Tu H, et al. Effects of cell-type specific leptin receptor mutation on leptin transport across the BBB. Peptides. 2011;32(7):1392-1399.
  • Lloret A, Monllor P, Esteve D, Cervera-Ferri A, Lloret A. Obesity as a risk factor for Alzheimer’s disease: implication of leptin and glutamate. Front Neurosci. 2019;13:508.
  • Li S, Li X. Leptin in normal physiology and leptin resistance. Sci Bull. 2016;61(19):1480-1488.
  • Arnoldussen IA, Kiliaan AJ, Gustafson DR. Obesity and dementia: adipokines interact with the brain. Eur Neuropsychopharmacol. 2014;24(12):1982-1999.
  • Fruhwürth S, Vogel H, Schürmann A, Williams KJ. Novel insights into how overnutrition disrupts the hypothalamic actions of leptin. Front Endocrinol. 2018;9:89.
  • McGregor G, Harvey J. Regulation of hippocampal synaptic function by the metabolic hormone, leptin: implications for health and neurodegenerative disease. Front Cell Neurosci. 2018; 12:340.
  • 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(1):67.
  • McGuire MJ, Ishii M. Leptin dysfunction and Alzheimer’s disease: evidence from cellular, animal, and human studies. Cell Mol Neurobiol. 2016;36(2):203-217.
  • Mejido DC, Peny JA, Vieira MN, Ferreira ST, De Felice FG. Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer’s disease. Neuropharmacol. 2020; 171:108115.
  • Khant Aung Z, Ladyman SR, Brown RSE. Transient loss of satiety effects of leptin in middle-aged male mice. J Neuroendocrinol. 2024;36(5):e13386.
  • Maric I, Krieger JP, van der Velden P, et al. Sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents. Front Nutr. 2022;9:828522.
  • Aragonès G, Ardid‐Ruiz A, Ibars M, Suárez M, Bladé C. Modulation of leptin resistance by food compounds. Mol Nutr Food Res. 2016;60(8):1789-1803.
  • Fujita Y, Yamashita T. The effects of leptin on glial cells in neurological diseases. Front Neurosci. 2019;13:828.
  • Grizzanti J, Lee HG, Camins A, Pallas M, Casadesus G. The therapeutic potential of metabolic hormones in the treatment of age-related cognitive decline and Alzheimer’s disease. Nutr Res. 2016;36(12):1305-1315.
  • Paz-Filho GJ. The effects of leptin replacement on neural plasticity. Neural Plast. 2016;2016:8528934.
  • Forny-Germano L, De Felice FG, Vieira MNDN. The role of leptin and adiponectin in obesity-associated cognitive decline and Alzheimer’s disease. Front Neurosci. 2019;12:1027.
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Year 2024, Volume: 7 Issue: 3, 346 - 351, 27.05.2024
https://doi.org/10.32322/jhsm.1462938

Abstract

References

  • GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7(2):e105-e125. doi: 10.1016/S2468-2667(21)00249-8
  • World Health Organization. Obesity and overweight. Updated 2021. Accessed July 28, 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  • Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017;13(4):851-863. doi:10.5114/aoms.2016.58928
  • Moser VA, Christensen A, Liu J, et al. Effects of aging, high-fat diet, and testosterone treatment on neural and metabolic outcomes in male brown Norway rats. Neurobiol Aging. 2019; 73:145-160. doi: 10.1016/j.neurobiolaging.2018.09.016
  • Loffredo L, Ettorre E, Zicari AM, et al. Oxidative stress and gut-derived lipopolysaccharides in neurodegenerative disease: role of NOX2. Oxid Med Cell Longev. 2020;2020:8630275. doi: 10.1155/2020/8630275
  • Forsythe P, Bienenstock J, Kunze WA. Vagal pathways for microbiome-brain-gut axis communication. Adv Exp Med Biol. 2014;817:115-133. doi: 10.1007/978-1-4939-0897-4_5
  • Isidori AM, Strollo F, Morè M, et al. Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab. 2000;85(5):1954-1962.
  • van Andel M, van Schoor NM, Korten NC, Comijs HC, Heijboer AC, Drent ML. The association between high-molecular-weight adiponectin, ghrelin and leptin and age-related cognitive decline: results from longitudinal aging study Amsterdam. J Gerontol A Biol Sci Med Sci. 2021;76(1):131-140.
  • Nguyen TT, Ta QTH, Nguyen TKO, Nguyen TTD, Van Giau V. Type 3 diabetes and its role implications in Alzheimer’s disease. Int J Mol Sci. 2020;21(9):3165. doi: 10.3390/ijms21093165
  • Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer’s disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1078-1089. doi: 10.1016/j.bbadis.2016. 08.018
  • Selman A, Burns S, Reddy AP, Culberson J, Reddy PH. The role of obesity and diabetes in dementia. Int J Mol Sci. 2022;23(16):9267. doi: 10.3390/ijms23169267
  • Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-1143.
  • Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-867.
  • Bowman K, Thambisetty M, Kuchel GA, Ferrucci L, Melzer D. Obesity and longer term risks of dementia in 65–74 year olds. Age Ageing. 2019;48(3):367-373. doi: 10.1093/ageing/afz020
  • Joo SH, Yun SH, Kang DW, Hahn CT, Lim HK, Lee CU. Body mass index in mild cognitive impairment according to age, sex, cognitive intervention, and hypertension and risk of progression to Alzheimer’s disease. Front Psychiatry. 2018;9:142. doi: 10.3389/fpsyt.2018.00142
  • Wu H, Ghosh S, Perrard XD, et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 2007; 115(8):1029-1038.
  • Kiliaan AJ, Arnoldussen IA, Gustafson DR. Adipokines: a link between obesity and dementia? Lancet Neurol. 2014;13(9):913-923.
  • Emmerzaal TL, Kiliaan AJ, Gustafson DR. 2003-2013: a decade of body mass index, Alzheimer’s disease, and dementia. J Alzheimers Dis. 2015;43(3):739-755.
  • García-Ptacek S, Faxén-Irving G, Čermáková P, Eriksdotter M, Religa D. Body mass index in dementia. Eur J Clin Nutr. 2014; 68(11):1204-1209.
  • Abbott RD, Ross GW, White LR, et al. Midlife adiposity and the future risk of Parkinson’s disease. Neurology. 2002;59(7):1051-1057.
  • Procaccini C, Santopaolo M, Faicchia D, et al. Role of metabolism in neurodegenerative disorders. Metabolism. 2016;65(9):1376-1390.
  • Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am J Clin Nutr. 2005;81(6):1335-1341.
  • Beyer F, Kharabian Masouleh S, Kratzsch J, et al. A metabolic obesity profile is associated with decreased gray matter volume in cognitively healthy older adults. Front Aging Neurosci. 2019; 11:202.
  • Hou Q, Guan Y, Yu W, et al. Associations between obesity and cognitive impairment in the Chinese elderly: an observational study. Clin Interv Aging. 2019;14:367-373.
  • Pannacciulli N, Del Parigi A, Chen K, Le DSN, Reiman EM, Tataranni PA. Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage. 2006;31(4):1419-1425.
  • Gunstad J, Paul RH, Cohen RA, Tate DF, Spitznagel MB, Gordon E. Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry. 2007;48(1):57-61.
  • Raji CA, Ho AJ, Parikshak NN, et al. Brain structure and obesity. Hum Brain Mapp. 2010;31(3):353-364.
  • Marqués-Iturria I, Pueyo R, Garolera M, et al. Frontal cortical thinning and subcortical volume reductions in early adulthood obesity. Psychiatry Res Neuroimaging. 2013;214(2):109-115.
  • Yokum S, Ng J, Stice E. Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes. 2012;36(5):656-664.
  • Debette S, Wolf C, Lambert JC, et al. Abdominal obesity and lower gray matter volume: a Mendelian randomization study. Neurobiol Aging. 2014;35(2):378-386.
  • Veit R, Kullmann S, Heni M, et al. Reduced cortical thickness associated with visceral fat and BMI. NeuroImage Clin. 2014; 6:307-311.
  • Pistell PJ, Morrison CD, Gupta S, et al. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol. 2010;219(1-2):25-32.
  • Winocur G, Greenwood CE. Studies of the effects of high fat diets on cognitive function in a rat model. Neurobiol Aging. 2005;26(1):46-49.
  • Wong Zhang DE, Tran V, Vinh A, et al. Pathophysiological links between obesity and dementia. Neuromolecular Med. 2023; 25(4):451-456.
  • Kothari V, Luo Y, Tornabene T, et al. High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochim Biophys Acta Mol Basis Dis. 2017;1863(2):499-508.
  • Saiyasit N, Chunchai T, Prus D, et al. Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet-induced obese condition. Nutrition. 2020;69:110576.
  • Hajiluian G, Abbasalizad Farhangi M, Nameni G, Shahabi P, Megari-Abbasi M. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats. Nutr Neurosci. 2018;21(10):744-752.
  • Guo DH, Yamamoto M, Hernandez CM, Khodadadi H, Baban B, Stranahan AM. Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells. J Clin Invest. 2020;130(4):1961-1976.
  • Erichsen JM, Fadel JR, Reagan LP. Peripheral versus central insulin and leptin resistance: role in metabolic disorders, cognition, and neuropsychiatric diseases. Neuropharmacol. 2022;203:108877.
  • Tian J, Wang T, Jia K, Guo L, Swerdlow RH, Du H. Nonobese male patients with Alzheimer’s disease are vulnerable to decrease in plasma leptin. J Alzheimers Dis. 2022;88(3):1017-1027.
  • Wang R, Yu C, Tang Z, et al. Leptin induces altered differentiation of keratinocytes by inducing insulin resistance: implications for metabolic syndrome-induced resistance of psoriatic therapy. J Dermatolog Treat. 2024;35(1):2309305.
  • Turner A, Hoyos C, Mowszowski L, et al. Obesity and oxidative stress in older adults at risk for dementia: a magnetic resonance spectroscopy study. Alzheimer Dis Assoc Disord. 2021;35(2):121-127.
  • Vamanu E, Rai SN. The link between obesity, microbiota dysbiosis, and neurodegenerative pathogenesis. Diseases. 2021;9(3):45.
  • Wieczorek M, Swiergiel AH, Pournajafi-Nazarloo H, Dunn AJ. Physiological and behavioral responses to interleukin-1β and LPS in vagotomized mice. Physiol Behav. 2005;85(4):500-511.
  • Casado ME, Collado-Pérez R, Frago LM, Barrios V. Recent advances in the knowledge of the mechanisms of leptin physiology and actions in neurological and metabolic pathologies. Int J Mol Sci. 2023;24(2):1422.
  • Lindhorst A, Raulien N, Wieghofer P, et al. Adipocyte death triggers a pro-inflammatory response and induces metabolic activation of resident macrophages. Cell Death Dis. 2021; 12(6):579.
  • Wu D, Molofsky AB, Liang HE, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332(6026):243-247.
  • Frühbeck G. Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol Biol. 2008;456:1-22.
  • Fietta P, Delsante G. Focus on adipokines. Theor Biol Forum. 2013;106(1-2):103-129.
  • Paul RF, Hassan M, Nazar HS, Gillani S, Afzal N, Qayyum I. Effect of body mass index on serum leptin levels. J Ayub Med Coll Abbottabad. 2011;23(3):40-43.
  • Kennedy A, Gettys TW, Watson P, et al. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab. 1997;82(4):1293-1300.
  • Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest. 1996;97(5):1344-1347.
  • Wada N, Hirako S, Takenoya F, Kageyama H, Okabe M, Shioda S. Leptin and its receptors. J Chem Neuroanat. 2014;61:191-199.
  • Hsuchou H, Kastin AJ, Tu H, et al. Effects of cell-type specific leptin receptor mutation on leptin transport across the BBB. Peptides. 2011;32(7):1392-1399.
  • Lloret A, Monllor P, Esteve D, Cervera-Ferri A, Lloret A. Obesity as a risk factor for Alzheimer’s disease: implication of leptin and glutamate. Front Neurosci. 2019;13:508.
  • Li S, Li X. Leptin in normal physiology and leptin resistance. Sci Bull. 2016;61(19):1480-1488.
  • Arnoldussen IA, Kiliaan AJ, Gustafson DR. Obesity and dementia: adipokines interact with the brain. Eur Neuropsychopharmacol. 2014;24(12):1982-1999.
  • Fruhwürth S, Vogel H, Schürmann A, Williams KJ. Novel insights into how overnutrition disrupts the hypothalamic actions of leptin. Front Endocrinol. 2018;9:89.
  • McGregor G, Harvey J. Regulation of hippocampal synaptic function by the metabolic hormone, leptin: implications for health and neurodegenerative disease. Front Cell Neurosci. 2018; 12:340.
  • 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(1):67.
  • McGuire MJ, Ishii M. Leptin dysfunction and Alzheimer’s disease: evidence from cellular, animal, and human studies. Cell Mol Neurobiol. 2016;36(2):203-217.
  • Mejido DC, Peny JA, Vieira MN, Ferreira ST, De Felice FG. Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer’s disease. Neuropharmacol. 2020; 171:108115.
  • Khant Aung Z, Ladyman SR, Brown RSE. Transient loss of satiety effects of leptin in middle-aged male mice. J Neuroendocrinol. 2024;36(5):e13386.
  • Maric I, Krieger JP, van der Velden P, et al. Sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents. Front Nutr. 2022;9:828522.
  • Aragonès G, Ardid‐Ruiz A, Ibars M, Suárez M, Bladé C. Modulation of leptin resistance by food compounds. Mol Nutr Food Res. 2016;60(8):1789-1803.
  • Fujita Y, Yamashita T. The effects of leptin on glial cells in neurological diseases. Front Neurosci. 2019;13:828.
  • Grizzanti J, Lee HG, Camins A, Pallas M, Casadesus G. The therapeutic potential of metabolic hormones in the treatment of age-related cognitive decline and Alzheimer’s disease. Nutr Res. 2016;36(12):1305-1315.
  • Paz-Filho GJ. The effects of leptin replacement on neural plasticity. Neural Plast. 2016;2016:8528934.
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There are 74 citations in total.

Details

Primary Language English
Subjects Health Promotion
Journal Section Review
Authors

Enes Kara 0000-0001-8784-1133

Şevval Işıklı 0009-0002-2659-7928

Publication Date May 27, 2024
Submission Date April 1, 2024
Acceptance Date May 15, 2024
Published in Issue Year 2024 Volume: 7 Issue: 3

Cite

AMA Kara E, Işıklı Ş. Obesity’s cognitive consequences: leptin’s influence on dementia. J Health Sci Med / JHSM. May 2024;7(3):346-351. doi:10.32322/jhsm.1462938

Interuniversity Board (UAK) Equivalency: Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS].

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Note: Our journal is not WOS indexed and therefore is not classified as Q.

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The indexes of the journal are ULAKBİM TR Dizin, Index Copernicus, ICI World of Journals, DOAJ, Directory of Research Journals Indexing (DRJI), General Impact Factor, ASOS Index, WorldCat (OCLC), MIAR, EuroPub, OpenAIRE, Türkiye Citation Index, Türk Medline Index, InfoBase Index, Scilit, etc.

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The platforms of the journal are Google Scholar, CrossRef (DOI), ResearchBib, Open Access, COPE, ICMJE, NCBI, ORCID, Creative Commons, etc.

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Our Journal using the DergiPark system indexed are;

Ulakbim TR Dizin,  Index Copernicus, ICI World of JournalsDirectory of Research Journals Indexing (DRJI), General Impact FactorASOS Index, OpenAIRE, MIAR,  EuroPub, WorldCat (OCLC)DOAJ,  Türkiye Citation Index, Türk Medline Index, InfoBase Index


Our Journal using the DergiPark system platforms are;

Google, Google Scholar, CrossRef (DOI), ResearchBib, ICJME, COPE, NCBI, ORCID, Creative Commons, Open Access, and etc.


Journal articles are evaluated as "Double-Blind Peer Review". 

Our journal has adopted the Open Access Policy and articles in JHSM are Open Access and fully comply with Open Access instructions. All articles in the system can be accessed and read without a journal user.  https//dergipark.org.tr/tr/pub/jhsm/page/9535

Journal charge policy   https://dergipark.org.tr/tr/pub/jhsm/page/10912


Editor List for 2022

Assoc. Prof. Alpaslan TANOĞLU (MD)  

Prof. Aydın ÇİFCİ (MD)

Prof. İbrahim Celalaettin HAZNEDAROĞLU (MD)

Prof. Murat KEKİLLİ (MD)

Prof. Yavuz BEYAZIT (MD) 

Prof. Ekrem ÜNAL (MD)

Prof. Ahmet EKEN (MD)

Assoc. Prof. Ercan YUVANÇ (MD)

Assoc. Prof. Bekir UÇAN (MD) 

Assoc. Prof. Mehmet Sinan DAL (MD)


Our journal has been indexed in DOAJ as of May 18, 2020.

Our journal has been indexed in TR-Dizin as of March 12, 2021.


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Articles published in the Journal of Health Sciences and Medicine have open access and are licensed under the Creative Commons CC BY-NC-ND 4.0 International License.