Progress of olfactory changes in metabolic diseases and the mechanisms

doi:10.3969/j.issn.1674-8115.2024.01.015

Abstract

Abstract:

Metabolic disorders, characterized by a complex pathogenesis, are experiencing a rising prevalence globally and a trend toward younger populations, making them a significant public health concern. Olfaction, a crucial sensory function, plays a pivotal role in an individual′s nutrition and quality of life. There is a bidirectional relationship between obesity and olfactory function. Olfaction is influenced by nutritional status; simultaneously, it plays a vital role in the regulation of food intake, energy expenditure, and lipid metabolism. Moreover, individuals with metabolic disorders such as type 2 diabetes and obstructive sleep apnea syndrome exhibit olfactory dysfunction. Mechanisms underlying olfactory changes in metabolic disorders involve alterations in metabolic states such as hyperglycemia and insulin resistance. These changes can lead to dysregulation of peptide hormones, adipocyte factors, and neurotransmitters, which may potentially act as mediators between metabolic disorders and olfactory dysfunction. Vascular and neural alterations resulting from metabolic disorders can directly damage olfactory nerves or induce abnormal neural transmission. Furthermore, dysbiosis in the gut microbiota induced by metabolic disorders is a potential mechanism for olfactory dysfunction. Cognitive dysfunction is a significant complication of metabolic disorders. Olfactory dysfunction can serve as an early clinical manifestation of cognitive impairment and contributes to early identification and assessment of diseases. This article reviews recent researches on the relationship between metabolic diseases and olfactory changes and the potential mechanisms.

Key words: obesity, diabetes mellitus, olfactory function, metabolic diseases, cognitive impairment

CLC Number:

R589

WU Qian, LI Huating. Progress of olfactory changes in metabolic diseases and the mechanisms[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(1): 131-136.

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References 61

1	The Lancet Diabetes Endocrinology. Obesity in China: time to act[J]. Lancet Diabetes Endocrinol, 2021, 9(7): 407.
2	WANG L M, PENG W, ZHAO Z P, et al. Prevalence and treatment of diabetes in China, 2013‒2018[J]. JAMA, 2021, 326(24): 2498-2506.
3	BOESVELDT S, DE GRAAF K. The differential role of smell and taste for eating behavior[J]. Perception, 2017, 46(3/4): 307-319.
4	DOTY R L. Olfactory dysfunction in Parkinson disease[J]. Nat Rev Neurol, 2012, 8(6): 329-339.
5	LAFAILLE-MAGNAN M E, POIRIER J, ETIENNE P, et al. Odor identification as a biomarker of preclinical AD in older adults at risk[J]. Neurology, 2017, 89(4): 327-335.
6	ZHANG Z, ZHANG B, WANG X, et al. Olfactory dysfunction mediates adiposity in cognitive impairment of type 2 diabetes: insights from clinical and functional neuroimaging studies[J]. Diabetes Care, 2019, 42(7): 1274-1283.
7	FIRESTEIN S. How the olfactory system makes sense of scents[J]. Nature, 2001, 413(6852): 211-218.
8	THIEBAUD N, JOHNSON M C, BUTLER J L, et al. Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning[J]. J Neurosci, 2014, 34(20): 6970-6984.
9	CAMPOLO J, CORRADI E, RIZZARDI A, et al. Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage Ⅰ‒Ⅱ obesity[J]. Eur Arch Otorhinolaryngol, 2021, 278(6): 2047-2054.
10	PENG M, COUTTS D, WANG T, et al. Systematic review of olfactory shifts related to obesity[J]. Obes Rev, 2019, 20(2): 325-338.
11	VELLUZZI F, DELEDDA A, ONIDA M, et al. Relationship between olfactory function and BMI in normal weight healthy subjects and patients with overweight or obesity[J]. Nutrients, 2022, 14(6): 1262.
12	HOLINSKI F, MENENAKOS C, HABER G, et al. Olfactory and gustatory function after bariatric surgery[J]. Obes Surg, 2015, 25(12): 2314-2320.
13	HANCI D, ALTUN H, ALTUN H, et al. Laparoscopic sleeve gastrectomy improves olfaction sensitivity in morbidly obese patients[J]. Obes Surg, 2016, 26(3): 558-562.
14	MAKARONIDIS J M, NEILSON S, CHEUNG W H, et al. Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: effect of gender, type 2 diabetes and relationship to post-operative weight loss[J]. Appetite, 2016, 107: 93-105.
15	ZERRWECK C, ZURITA L, ÁLVAREZ G, et al. Taste and olfactory changes following laparoscopic gastric bypass and sleeve gastrectomy[J]. Obes Surg, 2016, 26(6): 1296-1302.
16	ZERRWECK C, GALLARDO V C, CALLEJA C, et al. Gross olfaction before and after laparoscopic gastric bypass[J]. Obes Surg, 2017, 27(11): 2988-2992.
17	GUYOT E, DOUGKAS A, ROBERT M, et al. Food preferences and their perceived changes before and after bariatric surgery: a cross-sectional study[J]. Obes Surg, 2021, 31(7): 3075-3082.
18	RIERA C E, TSAOUSIDOU E, HALLORAN J, et al. The sense of smell impacts metabolic health and obesity[J]. Cell Metab, 2017, 26(1): 198-211.e5.
19	STAFFORD L D, WHITTLE A. Obese individuals have higher preference and sensitivity to odor of chocolate[J]. Chem Senses, 2015, 40(4): 279-284.
20	KINDLEYSIDES S, BECK K L, WALSH D C I, et al. Fat sensation: fatty acid taste and olfaction sensitivity and the link with disinhibited eating behaviour[J]. Nutrients, 2017, 9(8): 879.
21	POESSEL M, MORYS F, BREUER N, et al. Brain response to food odors is not associated with body mass index and obesity-related metabolic health measures[J]. Appetite, 2022, 168: 105774.
22	LE FLOCH J P, LE LIÈVRE G, LABROUE M, et al. Smell dysfunction and related factors in diabetic patients[J]. Diabetes Care, 1993, 16(6): 934-937.
23	WEINSTOCK R S, WRIGHT H N, SMITH D U. Olfactory dysfunction in diabetes mellitus[J]. Physiol Behav, 1993, 53(1): 17-21.
24	CATAMO E, TORNESE G, CONCAS M P, et al. Differences in taste and smell perception between type 2 diabetes mellitus patients and healthy controls[J]. Nutr Metab Cardiovasc Dis, 2021, 31(1): 193-200.
25	RASMUSSEN V F, VESTERGAARD E T, HEJLESEN O, et al. Prevalence of taste and smell impairment in adults with diabetes: a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES)[J]. Prim Care Diabetes, 2018, 12(5): 453-459.
26	KAYA K S, MAZı E E, DEMIR S T, et al. Relationship between progression of type 2 diabetes mellitus and olfactory function[J]. Am J Otolaryngol, 2020, 41(2): 102365.
27	MOZZANICA F, FERRULLI A, VUJOSEVIC S, et al. Olfactory disfunction and diabetic complications in type 2 diabetic patients: a pilot study[J]. Endocrine, 2022, 75(3): 760-767.
28	LI J, LI M Y, ZHANG J J, et al. Associations between taste and smell alterations and diabetes-related comorbidities among US adults: the National Health and Nutrition Examination Surveys 2011‒2014[J]. Acta Diabetol, 2022, 59(3): 429-433.
29	BOREL A L. Sleep apnea and sleep habits: relationships with metabolic syndrome[J]. Nutrients, 2019, 11(11): 2628.
30	MAGLIULO G, DE VINCENTIIS M, IANNELLA G, et al. Olfactory evaluation in obstructive sleep apnoea patients[J]. Acta Otorhinolaryngol Ital, 2018, 38(4): 338-345.
31	ARNOLD S E, ARVANITAKIS Z, MACAULEY-RAMBACH S L, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums[J]. Nat Rev Neurol, 2018, 14(3): 168-181.
32	BOSCO D, PLASTINO M, CRISTIANO D, et al. Dementia is associated with insulin resistance in patients with Parkinson′s disease[J]. J Neurol Sci, 2012, 315(1/2): 39-43.
33	DE LA MONTE S M, WANDS J R. Alzheimer′s disease is type 3 diabetes: evidence reviewed[J]. J Diabetes Sci Technol, 2008, 2(6): 1101-1113.
34	PONSEN M M, STOFFERS D, BOOIJ J, et al. Idiopathic hyposmia as a preclinical sign of Parkinson′s disease[J]. Ann Neurol, 2004, 56(2): 173-181.
35	TAHERI S, MAHMOODI M, OPACKA-JUFFRY J, et al. Distribution and quantification of immunoreactive orexin A in rat tissues[J]. FEBS Lett, 1999, 457(1): 157-161.
36	ZAGHLOUL H, PALLAYOVA M, AL-NUAIMI O, et al. Association between diabetes mellitus and olfactory dysfunction: current perspectives and future directions[J]. Diabet Med, 2018, 35(1): 41-52.
37	KOSSE C, GONZALEZ A, BURDAKOV D. Predictive models of glucose control: roles for glucose-sensing neurones[J]. Acta Physiol, 2015, 213(1): 7-18.
38	POESSEL M, FREIHERR J, WIENCKE K, et al. Insulin resistance is associated with reduced food odor sensitivity across a wide range of body weights[J]. Nutrients, 2020, 12(8): 2201.
39	FIGLEWICZ D P, IKEDA H, HUNT T R, et al. Brain insulin binding is decreased in Wistar Kyoto rats carrying the 'fa' gene[J]. Peptides, 1986, 7(1): 61-65.
40	EDWIN THANARAJAH S, HOFFSTALL V, RIGOUX L, et al. The role of insulin sensitivity and intranasally applied insulin on olfactory perception[J]. Sci Rep, 2019, 9(1): 7222.
41	MURATA K, KINOSHITA T, FUKAZAWA Y, et al. GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice[J]. Sci Rep, 2019, 9(1): 7132.
42	VÁRKONYI T, KÖREI A, PUTZ Z, et al. Olfactory dysfunction in diabetes: a further step in exploring central manifestations of neuropathy?[J]. Angiology, 2014, 65(10): 857-860.
43	DUDA-SOBCZAK A, ARASZKIEWICZ A, URBAS M, et al. Impaired olfactory function is related to the presence of neuropathy in adults with type 1 diabetes[J]. Diab Vasc Dis Res, 2017, 14(2): 139-143.
44	PALOUZIER-PAULIGNAN B, LACROIX M C, AIMÉ P, et al. Olfaction under metabolic influences[J]. Chem Senses, 2012, 37(9): 769-797.
45	FERNANDEZ-GARCIA J C, ALCAIDE J, SANTIAGO-FERNANDEZ C, et al. An increase in visceral fat is associated with a decrease in the taste and olfactory capacity[J]. PLoS One, 2017, 12(2): e0171204.
46	UYGUN B, KIYICI S, OZMEN S, et al. The association between olfaction and taste functions with serum ghrelin and leptin levels in obese women[J]. Metab Syndr Relat Disord, 2019, 17(9): 452-457.
47	FERNÁNDEZ-ARANDA F, AGÜERA Z, FERNÁNDEZ-GARCÍA J C, et al. Smell-taste dysfunctions in extreme weight/eating conditions: analysis of hormonal and psychological interactions[J]. Endocrine, 2016, 51(2): 256-267.
48	MUTLU A S, GAO S M, ZHANG H N, et al. Olfactory specificity regulates lipid metabolism through neuroendocrine signaling in Caenorhabditis elegans[J]. Nat Commun, 2020, 11(1): 1450.
49	FAN Y, PEDERSEN O. Gut microbiota in human metabolic health and disease[J]. Nat Rev Microbiol, 2021, 19(1): 55-71.
50	WONG A C N, WANG Q P, MORIMOTO J, et al. Gut microbiota modifies olfactory-guided microbial preferences and foraging decisions in Drosophila[J]. Curr Biol, 2017, 27(15): 2397-2404.e4.
51	FRANÇOIS A, GREBERT D, RHIMI M, et al. Olfactory epithelium changes in germfree mice[J]. Sci Rep, 2016, 6: 24687.
52	NAUDON L, FRANÇOIS A, MARIADASSOU M, et al. First step of odorant detection in the olfactory epithelium and olfactory preferences differ according to the microbiota profile in mice[J]. Behav Brain Res, 2020, 384: 112549.
53	O'DONNELL M P, FOX B W, CHAO P H, et al. A neurotransmitter produced by gut bacteria modulates host sensory behaviour[J]. Nature, 2020, 583(7816): 415-420.
54	CANI P D, BIBILONI R, KNAUF C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes, 2008, 57(6): 1470-1481.
55	BIESSELS G J, DESPA F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications[J]. Nat Rev Endocrinol, 2018, 14(10): 591-604.
56	TANAKA H, GOURLEY D D, DEKHTYAR M, et al. Cognition, brain structure, and brain function in individuals with obesity and related disorders[J]. Curr Obes Rep, 2020, 9(4): 544-549.
57	JUNG H J, SHIN I S, LEE J E. Olfactory function in mild cognitive impairment and Alzheimer′s disease: a meta-analysis[J]. Laryngoscope, 2019, 129(2): 362-369.
58	SANKE H, MITA T, YOSHII H, et al. Relationship between olfactory dysfunction and cognitive impairment in elderly patients with type 2 diabetes mellitus[J]. Diabetes Res Clin Pract, 2014, 106(3): 465-473.
59	YULUG B, SAATCI O, IŞIKLAR A, et al. The association between HbA1c levels, olfactory memory and cognition in normal, pre-diabetic and diabetic persons[J]. Endocr Metab Immune Disord Drug Targets, 2020, 20(2): 198-212.
60	SANKE H, MITA T, YOSHII H, et al. Olfactory dysfunction predicts the development of dementia in older patients with type 2 diabetes[J]. Diabetes Res Clin Pract, 2021, 174: 108740.
61	MARTINS I V A, RIVERS-AUTY J, ALLAN S M, et al. Mitochondrial abnormalities and synaptic loss underlie memory deficits seen in mouse models of obesity and Alzheimer′s disease[J]. J Alzheimers Dis, 2017, 55(3): 915-932.

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