TITLE: Obesity-associated olfact deficit and FMD
PARTICIPANTS: A group of obese and/or overweighted patients who did not pass screening criteria (BMI and/or neuropsychological testing) to undergo surgical procedure aimed at reducing weight (grastrectomy, bypass, other…)
STUDY: Patients will undergo – one month before and one month after the implementation of FMD (lasting 6 months) - a battery of:
- Olfactory test (sniffin’ stick test)
- Taste Test
- Neuropsychological tests: MMSE, TSK, HADS, DGI, usual gait speed, rapid gait speed, 400-m time, and Health ABC Physical Performance Battery (HABCPPB) score), total standing balance time, fine motor function (finger tapping time), and manual dexterity (Purdue Pegboard Test Termometro dello stress, California Verbal Learning Test [CVLT]), visuoperceptual speed (Digit Symbol Substitution Test [DSST]), executive function (Trail Making Test part B [TMT-B]), and attention (TMT-A)
- Blood Samples (IFOM – Milano)
LOCATION: Department of Clinical Sciences and Translational Medicine - ENT Unit, University of Rome Tor Vergata, ITER Center for Balance and Rehabilitation Research, Rome, Italy
RESEARCHER: Alessandro Micarelli (email@example.com), Marco Alessandrini, Beatrice Micarelli, Giovanni Cesana
SYNOPSIS: The increase of body weight is actually associated with a reduction in olfactory sensitivity and it has been already demonstrated that body mass and fasting states may interact in order to influence the olfactory sensitivity (Cameron JD, Goldfield GS, Doucet É. 2012. Fasting for 24 h improves nasal chemosensory performance and food palatability in a related manner. Appetite. 58(3):978–981; Palouzier-Paulignan B, Lacroix MC, Aimé P, Baly C, Caillol M, Congar P, Julliard AK, Tucker K, Fadool DA. 2012. Olfaction under metabolic influences. Chem Senses. 37(9):769–797.). In particular, differences in terms of olfactory detection and threshold found between fasting and satiety periods have demonstrated to be mainly pronounced with the increase of body weight (Pager J, Giachetti I, Holley A, Le Magnen J. 1972. A selective control of olfactory bulb electrical activity in relation to food deprivation and satiety in rats. Physiol Behav. 9(4):573–579.; Julliard AK, Chaput MA, Apelbaum A, Aim P. 2007. Changes in rat olfactory detection performance induced by orexin and leptin mimicking fasting and satiation. Behav Brain Res. 183:123–129.; Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA. 2009. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J Neurosci. 29(20):6734–6751.). Considering these aspects, it has been indicated that the grastric orexinergic peptide “GRELIN” behaves as an olfactory modulator between body weight and fasting state. Its receptor – indeed – is expresssed in the olfactory bulb and central infusion of GRELIN have been demonstrated to increase the detection of odorants in rodents (Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, et al. 2011. Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J Neurosci. 31(15):5841–5846.). At the same time obesity is associated with reduced hematic levels of GRELIN and it may modify the phasic suppression of this peptide after the meal (Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. 2001. Circulating ghrelin levels are decreased in human obesity. Diabetes. 50(4):707–709.; English P, Ghatei M, Malik I, Bloom S, Wilding J. 2002. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab. 87:2984–2987; Meyer-Gerspach AC, Wölnerhanssen B, Beglinger B, Nessenius F, Napitupulu M, Schulte FH, Steinert RE, Beglinger C. 2014. Gastric and intestinal satiation in obese and normal weight healthy people. Physiol Behav. 129:265–271.), even though this effect may vary depending on insulin sensitivity and macro-nutrient composition of the meal (Foster-Schubert KE, Overduin J, Prudom CE, Liu J, Callahan HS, Gaylinn BD, Thorner MO, Cummings DE. 2008. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 93(5):1971–1979.). Thus it has been further demonstrated that peripheral infusion of GRELIN increase the sniffing magnitude in healthy subjects and that BMI is associated to an higher influence of the internal state on the olfactory sensitivity and that these phenomena are partly due to a postprandial reactivity of GRELIN, which has been found altered in the obesity (Stafford LD, Welbeck K. 2011. High hunger state increases olfactory sensitivity to neutral but not food odors. Chem Senses. 36(2):189–198.; English P, Ghatei M, Malik I, Bloom S, Wilding J. 2002. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab. 87:2984–2987.). Finally, as most important point, the blood infusion of this peptide in sated subjects increase the neuronal responses to food-related stimuli in cortical areas correlated to nutrition and reward, possibly contributing to the revaluation of food, mimicking a fasting state, since that such infusion also induce an exploratory sniffing in both animal and human models (Goldstone AP, Prechtl CG, Scholtz S, Miras AD, Chhina N, Durighel G, Deliran SS, Beckmann C, Ghatei MA, Ashby DR, et al. 2014. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr. 99(6):1319–1330.; Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, et al. 2011. Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J Neurosci. 31(15):5841–5846.).
Thus, given these experiences strenghtening the association between olfactory sensitivity (and more in general olfactory behaviour), which depose for an association between obesity, olfaction and craving/rewarding phenomena, the aim of the present study is to test if obese subjects – not included in surgical procedures - may benefit from a mimicking fasting protocol in order to modify their binge-eating behaviour – by means of an uncoscious olfactory re-arrangement – and thus benefit from a “spontaneous” weight reduction.