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• Clinical Article •
The effect of leucine on feeding center and reward system in T2DM patients and healthy control subjects: a resting-state fMRI study
LI Mei-jiao  LIU Hua-sheng  GU Qian-biao  DENG Ling-ling  DUAN Jun-hong  LIANG Qi  RONG Peng-fei  WANG Wei 

DOI:10.12015/issn.1674-8034.2018.07.002.


[Abstract] Objective: To study the functional connectivity of the reward system and feeding center after oral leucine in type 2 diabetes mellitus by resting-state fMRI, and analyze the relationships between the changes and related metabolic indicators of T2DM during this test.Materials and Methods: This study included several T2DM patients (T2DM, n=9) whose age, sex, education match up with healthy control subjects (HC, n=8). Resting-state fMRI data were collected by blood oxygen level dependent sequence (BOLD). Brain regions involving in feeding center and reward system were selected as seeds, and functional connection values between these seeds and other voxels in the brain were calculated after oral leucine, the resulted values of both groups were compared using two-sample t-test to locate the regions with significant change. Then correlation analysis was conducted between clinical indexes and values of functional connection extracted from significant difference between groups.Results: After oral leucine, HC group people showed significantly increased functional connectivity between left orbitofrontal cortex and right cerebellum posterior lobe (P<0.05). The functional connection values between the prefrontal cortex, the anterior cingulum cortex, orbitofrontal cortex, limbic lobe and left putamen increased significantly (P<0.05), however there were no significant differences in T2DM group (P>0.05). Moreover, negative correlations were found between the changes of functional connection values of brain function and fasting serum insulin, HOMA2-IR in T2DM group (P< 0.05). Positively correlations were found between the changes of functional connection values of brain function and plasma leucine level in HC group (P<0.05).Conclusions: T2DM damage the functional connectivity of reward-associated brain regions, and the functional connectivity between left OFC and cerebellar tonsils was correlates with the degree of HOMA2-IR and fasting serum insulin. Moreover, this study indicated that central insulin resistance may damage the leucine sensing pathway.
[Keywords] Diabetes mellitus, Type 2；Leucine；Magnetic resonance imaging；Reward；Feeding center

LI Mei-jiao Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

LIU Hua-sheng Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

GU Qian-biao Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

DENG Ling-ling Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

DUAN Jun-hong Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

LIANG Qi Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

RONG Peng-fei Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

WANG Wei* Department of Radiology, the Third Xiangya Hospital of Central South University, Changsha 410013, China

*Correspondence to: Wang W, E-mail: cjr.wangwei@vip.163.com

Conflicts of interest   None.

ACKNOWLEDGMENTS  This work was part of project of National Key Clinical Specialty No. 2013-544 National Natural Science Foundation of China No. 81471715
Received  2018-03-07
Accepted  2018-05-15
DOI: 10.12015/issn.1674-8034.2018.07.002
DOI:10.12015/issn.1674-8034.2018.07.002.

[1]
Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol, 2002, 90(5A): 3G-10G.
[2]
Anthony K, Reed LJ, Dunn JT, et al. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome? Diabetes, 2006, 55(11): 2986-2992.
[3]
Macotela Y, Emanuelli B, Bång AM, et al. Dietary leucine: an environmental modifier of insulin resistance acting on multiple levels of metabolism. Plos One, 2011, 6(6): e21187.
[4]
Kahn BB, Myers MG Jr. mTOR tells the brain that the body is hungry. Nat Med, 2006, 12(6): 615-617.
[5]
Smith GI, Yoshino J, Stromsdorfer KL, et al. Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation. Diabetes, 2015, 64(5): 1555-1563.
[6]
Hägglund MG, Roshanbin S, Löfqvist E, et al. B(0)AT2 (SLC6A15) is localized to neurons and astrocytes, and is involved in mediating the effect of leucine in the brain. Plos One, 2013, 8(3): e58651.
[7]
Morrison CD, Xi X, White CL, et al. Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism. Am J Physiol Endocrinol Metab, 2007, 293(1): E165-171.
[8]
Cota D, Proulx K, Smith KA, et al. Hypothalamic mTOR signaling regulates food intake. Science, 2006, 312(5775): 927-930.
[9]
Heeley N, Blouet C. Central amino acid sensing in the control of feeding behavior. Front Endocrinol (Lausanne), 2016, 7: 148.
[10]
Laron Z. Insulin and the brain. Arch Physiol Biochem, 2009, 115(2): 112-116.
[11]
Kulve JS, Veltman DJ, Bloemendaal LV, et al. Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes. Diabetologia, 2015, 58(12): 2688-2698.
[12]
Choi YH, Chang N, Anderson GH. An intragastric amino acid mixture influences extracellular amino acid profiles in the lateral hypothalamic area of freely moving rats. Can J Physiol Pharmacol, 1999, 77(11): 827-834.
[13]
Rolls ET. Reward systems in the brain and nutrition. Annu Rev Nutr, 2016, 36: 435-470.
[14]
Silva AD, Salem V, Matthews PM, et al. The use of functional MRI to study appetite control in the CNS. Exp Diabetes Res, 2014, 2012(4-5): 764017.
[15]
Rolls ET. Taste, olfactory and food texture reward processing in the brain and the control of appetite. Proc Nutr Soc, 2012, 71(4): 488-501.
[16]
Stoeckel LE, Weller RE, Twieg DB, et al. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage, 2008, 41(2): 636-647.
[17]
Burger KS, Stice E. Relation of dietary restraint scores to activation of reward-related brain regions in response to food intake, anticipated intake, and food pictures. Neuroimage, 2011, 55(1): 233-239.
[18]
Rolls ET, Verhagen JV, Kadohisa M. Representations of the texture of food in the primate orbitofrontal cortex: neurons responding to viscosity, grittiness, and capsaicin. J Neurophysiol, 2003, 90(6): 3711-3724.
[19]
Volkow ND, Wang GJ, Baler AR. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci, 2011, 15(1): 37-46..
[20]
陈娟，刘珺，刘煌辉，等. 2型糖尿病患者眶额皮层相关功能连接的功能MRI研究．磁共振成像, 2017, 8(5): 321-326.
[21]
Chris M, Phan TG, Jian C, et al. Brain Atrophy in Type 2 Diabetes. Diabetes Care, 2013, 36(12): 4036-4042.
[22]
Öst A, Svensson K, Ruishalme I, et al. Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes. Mol Med, 2010, 16(7-8): 235-246.
[23]
Brännmark C, Nyman E, Fagerholm S, et al. Insulin signaling in type 2 diabetes. J Biol Chem, 2013, 288(14): 9867-9880.
[24]
ann SG, Selvaraj A, Thomas G. mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol Med, 2007, 13(6): 52-59
[25]
Pedroso JA, Zampieri TT, Donato JJ. Reviewing the effects of l-leucine supplementation in the regulation of food intake, energy balance, and glucose homeostasis. Nutrients, 2015, 7(5): 3914-3937.
[26]
Ropelle ER, Pauli JR, Fernandes MF, et al. A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss. Diabetes, 2008, 57(3): 594-605.
[27]
Smith GI, Yoshino J, Stromsdorfer KL, et al. Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation. Diabetes, 2015, 64(5): 1555-1563.
[28]
Heni M, Kullmann S, Ketterer C, et al. Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions. Diabetologia, 2012, 55(6): 1773-1782.
[29]
Steinert RE, Landrock MF, Ullrich SS, et al. Effects of intraduodenal infusion of the branched-chain amino acid leucine on ad libitum eating, gut motor and hormone functions, and glycemia in healthy men. Am J Clin Nutr, 2015, 102(4): 820-827.

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