药学学报, 2021, 56(4): 906-912
张宁宁, 王真真*, 陈乃宏*. 膳食脂肪酸与抑郁症的相关性及机制研究进展[J]. 药学学报, 2021, 56(4): 906-912.
ZHANG Ning-ning, WANG Zhen-zhen*, CHEN Nai-hong*. Association of depression with dietary fatty acids and the progress of mechanism research[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 906-912.

张宁宁, 王真真*, 陈乃宏*
中国医学科学院、北京协和医学院药物研究所, 神经科学中心, 北京 100050
关键词:    膳食脂肪      抑郁症      饱和脂肪酸      高脂饮食      肥胖     
Association of depression with dietary fatty acids and the progress of mechanism research
ZHANG Ning-ning, WANG Zhen-zhen*, CHEN Nai-hong*
Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Depression is one of the diseases with the highest disability rate in the world. A large number of studies have shown that the intake of unsaturated fatty acids can deal with depression while chronic overconsumption of saturated fatty acids is a risk factor for depression. It was suggested that the mechanism of saturated fatty acids inducing depression is related to the following four aspects:regulating the function which links to depression in whole brain and specific brain regions, including the hippocampus, the hypothalamic-pituitary-adrenal axis, the striatum, and the prefrontal cortex; stimulating the secretion of inflammatory factors; affecting the balance and function of metabolic regulatory hormones, including leptin, adiponectin, glucocorticoid, and insulin; inducing the disturbance of intestinal flora. This article reviews the relationship between dietary fatty acids and depression, and the possible mechanisms by which saturated fatty acids induce depression from the four aspects mentioned above.
Key words:    dietary fat    depression    saturated fatty acid    high-fat diet    obesity   
收稿日期: 2020-09-16
DOI: 10.16438/j.0513-4870.2020-1492
基金项目: 国家自然科学基金资助项目(81773924);北京市自然科学基金资助项目(7182114).
通讯作者: 王真真,Tel:86-10-63165182,E-mail:wangzz@imm.ac.cn;陈乃宏,Tel:86-10-63165177,E-mail:chennh@imm.ac.cn
Email: wangzz@imm.ac.cn;chennh@imm.ac.cn
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陈乃宏*  在本刊中的所有文章

[1] Czeh B, Fuchs E, Wiborg O, et al. Animal models of major depression and their clinical implications[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2016, 64:293-310.
[2] Fernandes MF, Mutch DM, Leri F. The relationship between fatty acids and different depression-related brain regions, and their potential role as biomarkers of response to antidepressants[J]. Nutrients, 2017, 9:298.
[3] Tsuboi H, Watanabe M, Kobayashi F, et al. Associations of depressive symptoms with serum proportions of palmitic and arachidonic acids, and alphatocopherol effects among malepopulation——a preliminary study[J]. Clin Nutr, 2013, 32:289-293.
[4] Fatemi F, Siassi F, Qorbani M, et al. Higher dietary fat quality is associated with lower anxiety score in women:a cross-sectional study[J]. Ann Gen Psychiatry, 2020, 19:14.
[5] Wolfe AR, Ogbonna EM, Lim S, et al. Dietary linoleic and oleic fatty acids in relation to severe depressed mood:10 years follow-up of a national cohort[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2009, 33:972-977.
[6] Macht M. How emotions affect eating:a five-way model[J]. Appetite, 2008, 50:1-11.
[7] Juruena MF, Cleare AJ. Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome[J]. Braz J Psychiatry, 2007, 29Suppl 1:S19-S26.
[8] Maniam J, Morris MJ. Palatable cafeteria diet ameliorates anxiety and depression like symptoms following an adverse early environment[J]. Psychoneuroendocrinology, 2010, 35:717-728.
[9] Hryhorczuk C, Sharma S, Fulton SE. Metabolic disturbances connecting obesity and depression[J]. Front Neurosci, 2013, 7:177.
[10] Singh M. Mood, food, and obesity[J]. Front Psychol, 2014, 5:925.
[11] Peet M, Murphy B, Shay J, et al. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients[J]. Biol Psychiatry, 1998, 43:315-319.
[12] Levant B. N-3(omega-3) polyunsaturated fatty acids in the pathophysiology and treatment of depression:pre-clinical evidence[J]. CNS Neurol Disord Drug Targets, 2013, 12:450-459.
[13] Lopes PA, Bandarra NM, Martins SV, et al. Markers of neuroprotection of combined EPA and DHA provided by fish oil are higher than those of EPA (Nannochloropsis) and DHA (Schizochytrium) from microalgae oils in Wistar rats[J]. Nutr Metab (Lond), 2017, 14:62.
[14] Demers G, Roy J, Machuca-Parra AI, et al. Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice[J]. Int J Obes (Lond), 2020, 44:1936-1945.
[15] Naliwaiko K, Araujo RL, Da Fonseca RV, et al. Effects of fish oil on the central nervous system:a new potential antidepressant?[J]. Nutr Neurosci, 2004, 7:91-99.
[16] Vetrivel U, Ravichandran SB, Kuppan K, et al. Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation[J]. Lipids Health Dis, 2012, 11:109.
[17] Thesing CS, Bot M, Milaneschi Y, et al. Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders[J]. Psychoneuroendocrinology, 2018, 87:53-62.
[18] Lai JS, Oldmeadow C, Hure AJ, et al. Inflammation mediates the association between fatty acid intake and depression in older men and women[J]. Nutr Res, 2016, 36:234-245.
[19] Sharma S, Fulton S. Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry[J]. Int J Obes (Lond), 2013, 37:382-389.
[20] Nakajima S, Fukasawa K, Gotoh M, et al. Saturated fatty acid is a principal cause of anxiety-like behavior in diet-induced obese rats in relation to serum lysophosphatidyl choline level[J]. Int J Obes (Lond), 2020, 44:727-738.
[21] Lin YS, Shao P, Zhou YL. The effects of high-fat diet during pregnancy and lactation on the behaviors and learning memory in adult male offspring[J]. Chin J Behav Med Brain Sci (中华行为医学与脑科学杂志), 2015, 2:101-104.
[22] Abbott SK, Else PL, Atkins TA, et al. Fatty acid composition of membrane bilayers:importance of diet polyunsaturated fat balance[J]. Biochim Biophys Acta, 2012, 1818:1309-1317.
[23] Muller CP, Reichel M, Muhle C, et al. Brain membrane lipids in major depression and anxiety disorders[J]. Biochim Biophys Acta, 2015, 1851:1052-1065.
[24] Park HR, Park M, Choi J, et al. A high-fat diet impairs neurogenesis:involvement of lipid peroxidation and brain-derived neurotrophic factor[J]. Neurosci Lett, 2010, 482:235-239.
[25] Lee BH, Kim YK. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment[J]. Psychiatry Investig, 2010, 7:231-235.
[26] Gupta S, Knight AG, Gupta S, et al. Saturated long-chain fatty acids activate inflammatory signaling in astrocytes[J]. J Neurochem, 2012, 120:1060-1071.
[27] Kleinridders A, Schenten D, Konner AC, et al. MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity[J]. Cell Metab, 2009, 10:249-259.
[28] Schriber RA, Anbari Z, Robins RW, et al. Hippocampal volume as an amplifier of the effect of social context on adolescent depression[J]. Clin Psychol Sci, 2017, 5:632-649.
[29] Wu H, Liu Q, Kalavagunta PK, et al. Normal diet vs high fat diet-a comparative study:behavioral and neuroimmunological changes in adolescent male mice[J]. Metab Brain Dis, 2018, 33:177-190.
[30] Tsai SF, Wu HT, Chen PC, et al. High-fat diet suppresses the astrocytic process arborization and downregulates the glial glutamate transporters in the hippocampus of mice[J]. Brain Res, 2018, 1700:66-77.
[31] Contreras A, Del Rio D, Martinez A, et al. Inhibition of hippocampal long-term potentiation by high-fat diets:is it related to an effect of palmitic acid involving glycogen synthase kinase-3?[J]. Neuroreport, 2017, 28:354-359.
[32] Vagena E, Ryu JK, Baeza-Raja B, et al. A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling[J]. Transl Psychiatry, 2018, 9:141.
[33] Gabbay V, Ely BA, Li Q, et al. Striatum-based circuitry of adolescent depression and anhedonia[J]. J Am Acad Child Adolesc Psychiatry, 2013, 52:628-641.e13.
[34] Du Bois TM, Deng C, Bell W, et al. Fatty acids differentially affect serotonin receptor and transporter binding in the rat brain[J]. Neuroscience, 2006, 139:1397-1403.
[35] Meyer JH, Mcmain S, Kennedy SH, et al. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm[J]. Am J Psychiatry, 2003, 160:90-99.
[36] Pandya M, Altinay M, Malone DA, et al. Where in the brain is depression?[J]. Curr Psychiatry Rep, 2012, 14:634-642.
[37] Guida F, Luongo L, Marmo F, et al. Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice[J]. Mol Brain, 2015, 8:47.
[38] Dantzer R, O'connor JC, Freund GG, et al. From inflammation to sickness and depression:when the immune system subjugates the brain[J]. Nat Rev Neurosci, 2008, 9:46-56.
[39] Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychop-harmacology:translational implications of the impact of inflammation on behavior[J]. Neuropsychopharmacology, 2012, 37:137-162.
[40] Masson CJ, Mensink RP. Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men[J]. J Nutr, 2011, 141:816-821.
[41] Dunn AJ, Swiergiel AH, De Beaurepaire R. Cytokines as mediators of depression:what can we learn from animal studies?[J]. Neurosci Biobehav Rev, 2005, 29:891-909.
[42] Decarie-Spain L, Sharma S, Hryhorczuk C, et al. Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat[J]. Mol Metab, 2018, 10:1-13.
[43] Hamer M, Batty GD, Kivimaki M. Risk of future depression in people who are obese but metabolically healthy:the English longitudinal study of ageing[J]. Mol Psychiatry, 2012, 17:940-945.
[44] Gancheva S, Galunska B, Zhelyazkova-Savova M. Diets rich in saturated fat and fructose induce anxiety and depression-like behaviours in the rat:is there a role for lipid peroxidation?[J]. Int J Exp Pathol, 2017, 98:296-306.
[45] Myers MG,Jr., Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance[J]. Cell Metab, 2012, 15:150-156.
[46] Yamada N, Katsuura G, Ochi Y, et al. Impaired CNS leptin action is implicated in depression associated with obesity[J]. Endocrinology, 2011, 152:2634-2643.
[47] Turer AT, Scherer PE. Adiponectin:mechanistic insights and clinical implications[J]. Diabetologia, 2012, 55:2319-2326.
[48] Doumatey AP, Bentley AR, Zhou J, et al. Paradoxical hyperadiponectinemia is associated with the metabolically healthy obese (MHO) phenotype in African Americans[J]. J Endocrinol Metab, 2012, 2:51-65.
[49] Liu J, Guo M, Zhang D, et al. Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity[J]. Proc Natl Acad Sci U S A, 2012, 109:12248-12253.
[50] Nicolaides NC, Kyratzi E, Lamprokostopoulou A, et al. Stress, the stress system and the role of glucocorticoids[J]. Neuroimmunomodulation, 2015, 22:6-19.
[51] Brown ES, Varghese FP, Mcewen BS. Association of depression with medical illness:does cortisol play a role?[J]. Biol Psychiatry, 2004, 55:1-9.
[52] Sun Y, Wei C, Li HR, et al. Research progress on obesity-induced insulin resistance[J]. Chin J Gerontol (中国老年医学杂志), 2015, 35:6268-6271.
[53] Zagon A. Does the vagus nerve mediate the sixth sense[J]. Trends Neurosci, 2001, 24:671-673.
[54] Ma Y, Guo LN, Liu YL. Research progress of intestinal flora and occurrence of depression[J]. J Pract Med (实用医学杂志), 2018, 34:324-327.
[55] Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes[J]. Science, 2011, 334:105-108.
[56] Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity[J]. Gastroenterology, 2009, 137:1716-1724.e1-2.
[57] Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance[J]. Diabetes, 2007, 56:1761-1772.
[58] Wang Y, Ghoshal S, Ward M, et al. Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen (ovalbumin) in mice[J]. PLoS One, 2009, 4:e8442.
[59] Cani PD, Delzenne NM. The gut microbiome as therapeutic target[J]. Pharmacol Ther, 2011, 130:202-212.
[60] Devkota S, Wang Y, Musch MW, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice[J]. Nature, 2012, 487:104-108.
[61] Zhu X, Lin Y, Zhang J, et al. Thiazolidinediones, a class of anti-diabetic drugs, inhibit Id2 expression through a PPARgamma-independent pathway in human aortic smoothmuscle cells[J]. Cell Mol Life Sci, 2003, 60:212-218.
[62] Ohland CL, Pankiv E, Baker G, et al. Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism[J]. Nutr Neurosci, 2016, 19:337-345.
[63] Lindseth G, Petros T. Neurobehavioral effects of consuming dietary fatty acids[J]. Biol Res Nurs, 2016, 18:573-581.
[64] Vermeulen E, Stronks K, Snijder MB, et al. A combined high-sugar and high-saturated-fat dietary pattern is associated with more depressive symptoms in a multiethnic p-opulation:the HELIUS (Healthy Life in an Urban Setting) study[J]. Public Health Nutr, 2017, 20:2374-2382.
[65] Sanchez-Villegas A, Martinez-Gonzalez MA. Diet, a new target to prevent depression?[J]. BMC Med, 2013, 11:3.