Skip to main content
SpringerLink
Log in

Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5 % in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5 % increase in the expression levels of IRS-1, a 47.8 % decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg−1 d−1) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin improves cognitive functions in HFD-induced obese mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

AMPK:

AMP-activated protein kinase

GSK3β:

Glycogen synthase kinase-3β

HFD:

High-fat diet

IRS-1:

Insulin receptor substrate 1

MMP:

Mitochondrial membrane potential

ROS:

Reactive oxygen species

References

  • Arnold SE, Lucki I, Brookshire BR, Carlson GC, Browne CA, Kazi H et al (2014) High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice. Neurobiol Dis 67:79–87

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S (2011) Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol 68:51–57

    Article  PubMed Central  PubMed  Google Scholar 

  • Benedict C, Hallschmid M, Schultes B, Born J, Kern W (2007) Intranasal insulin to improve memory function in humans. Neuroendocrinology 86:136–142

    Article  CAS  PubMed  Google Scholar 

  • Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 1:1306–1311

    Article  PubMed  Google Scholar 

  • Brown MR, Geddes JW, Sullivan PG (2004) Brain region-specific, age-related, alterations in mitochondrial responses to elevated calcium. J Bioenerg Biomembr 36:401–406

    Article  CAS  PubMed  Google Scholar 

  • Buhl ES, Jessen N, Pold R, Ledet T, Flyvbjerg A, Pedersen SB, Pedersen O, Schmitz O, Lund S (2002) Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes 51:2199–2206

    Article  CAS  PubMed  Google Scholar 

  • Chiu SL, Chen CM, Cline HT (2008) Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron 58:708–719

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi SH, Kim YW, Kim SG (2010) AMPK-mediated GSK3beta inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress. Biochem Pharmacol 79:1352–1362

    Article  CAS  PubMed  Google Scholar 

  • Christie JM, Wenthold RJ, Monaghan DT (1999) Insulin causes a transient tyrosine phosphorylation of NR2A and NR2B NMDA receptor subunits in rat hippocampus. J Neurochem 72:1523–1528

    Article  CAS  PubMed  Google Scholar 

  • Clegg DJ, Gotoh K, Kemp C, Wortman MD, Benoit SC, Brown LM, D’Alessio D, Tso P, Seeley RJ, Woods SC (2011) Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol Behav 103:10–16

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Craft S (2005) Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging 26(Suppl 1):65–69

    Article  PubMed  Google Scholar 

  • Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A et al (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 69:29–38

    Article  PubMed Central  PubMed  Google Scholar 

  • Dash PK, Orsi SA, Moore AN (2006) Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway. J Neurosci 26:8048–8056

    Article  CAS  PubMed  Google Scholar 

  • Dong Y, Zhang M, Wang S, Liang B, Zhao Z, Liu C, Wu M, Choi HC, Lyons TJ, Zou MH (2010) Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes 59:1386–1396

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dong GZ, Jang EJ, Kang SH, Cho IJ, Park SD, Kim SC, Kim YW (2013) Red ginseng abrogates oxidative stress via mitochondria protection mediated by LKB1-AMPK pathway. BMC Complement Altern Med 13:64

    Article  PubMed Central  PubMed  Google Scholar 

  • Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, Bradshaw PC (2010) Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice. J Alzheimers Dis 20(Suppl 2):S535–S550

    PubMed  Google Scholar 

  • Finocchietto PV, Holod S, Barreyro F, Peralta JG, Alippe Y, Giovambattista A, Carreras MC, Poderoso JJ (2011) Defective leptin-AMP-dependent kinase pathway induces nitric oxide release and contributes to mitochondrial dysfunction and obesity in ob/ob mice. Antioxid Redox Signal 15:2395–2406

    Article  CAS  PubMed  Google Scholar 

  • Francis H, Stevenson R (2013) The longer-term impacts of Western diet on human cognition and the brain. Appetite 63:119–128

    Article  PubMed  Google Scholar 

  • Gaur V, Aggarwal A, Kumar A (2009) Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain. Eur J Pharmacol 616:147–154

    Article  CAS  PubMed  Google Scholar 

  • Gauthier MS, O’Brien EL, Bigornia S, Mott M, Cacicedo JM, Xu XJ, Gokce N, Apovian C, Ruderman N (2011) Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem Biophys Res Commun 404:382–387

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Greenwood CE, Winocur G (2005) High-fat diets, insulin resistance and declining cognitive function. Neurobiol Aging 26(Suppl 1):42–45

    Article  PubMed  Google Scholar 

  • Harmel E, Grenier E, Bendjoudi Ouadda A, El Chebly M, Ziv E, Beaulieu JF, Sane A, Spahis S, Laville M, Levy E (2014) AMPK in the small intestine in normal and pathophysiological conditions. Endocrinology 155:873–888

    Article  PubMed  Google Scholar 

  • Huang CC, Lee CC, Hsu KS (2004) An investigation into signal transduction mechanisms involved in insulin-induced long-term depression in the CA1 region of the hippocampus. J Neurochem 89:217–231

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Wu K, You Q, Huang R, Li S (2013) Naringin inhibits high glucose-induced cardiomyocyte apoptosis by attenuating mitochondrial dysfunction and modulating the activation of the p38 signaling pathway. Int J Mol Med 32:396–402

    CAS  PubMed  Google Scholar 

  • Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590

    Article  CAS  PubMed  Google Scholar 

  • Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE (2001) 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 276:46912–46916

    Article  CAS  PubMed  Google Scholar 

  • Johannsen DL, Ravussin E (2009) The role of mitochondria in health and disease. Curr Opin Pharmacol 9:780–786

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kanoski SE, Davidson TL (2011) Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 103:59–68

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kern W, Peters A, Fruehwald-Schultes B, Deininger E, Born J, Fehm HL (2001) Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 74:270–280

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Song JY, Park HJ, Park HK, Yun DH, Chung JH (2009) Naringin protects against rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Korean J Physiol Pharmacol 13:281–285

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kleinridders A, Ferris HA, Cai W, Kahn CR (2014) Insulin action in brain regulates systemic metabolism and brain function. Diabetes 63:2232–2243

    Article  PubMed Central  PubMed  Google Scholar 

  • Kola B, Christ-Crain M, Lolli F, Arnaldi G, Giacchetti G, Boscaro M, Grossman AB, Korbonits M (2008) Changes in adenosine 5′-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing’s syndrome. J Clin Endocrinol Metab 93:4969–4973

    Article  CAS  PubMed  Google Scholar 

  • Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB (2006) Increased malonyl-CoA and diacylglycerol content and reduced AMPK activity accompany insulin resistance induced by glucose infusion in muscle and liver of rats. Am J Physiol Endocrinol Metab 290:E471–E479

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Kumar A (2010) Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington’s like symptoms in rats: possible role of nitric oxide. Behav Brain Res 206:38–46

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Prakash A, Dogra S (2010) Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by d-galactose in mice. Food Chem Toxicol 48:626–632

    Article  CAS  PubMed  Google Scholar 

  • Laczo J, Vlcek K, Vyhnalek M, Vajnerova O, Ort M, Holmerova I, Tolar M, Andel R, Bojar M, Hort J (2009) Spatial navigation testing discriminates two types of amnestic mild cognitive impairment. Behav Brain Res 202:252–259

    Article  PubMed  Google Scholar 

  • Li H, Min Q, Ouyang C, Lee J, He C, Zou MH, Xie Z (2014) AMPK activation prevents excess nutrient-induced hepatic lipid accumulation by inhibiting mTORC1 signaling and endoplasmic reticulum stress response. Biochim Biophys Acta 1842:1844–1854

    Article  CAS  PubMed  Google Scholar 

  • Liang KC, Hon W, Tyan YM, Liao WL (1994) Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze. Chin J Physiol 37:201–212

    CAS  PubMed  Google Scholar 

  • Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S et al (2009) Reactive oxygen species enhance insulin sensitivity. Cell Metab 10:260–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McNeilly AD, Williamson R, Sutherland C, Balfour DJ, Stewart CA (2011) High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task. Behav Brain Res 217:134–141

    Article  CAS  PubMed  Google Scholar 

  • Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M (2005) Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4:119–125

    Article  CAS  PubMed  Google Scholar 

  • Mohlig M, Isken F, Ristow M (2004) Impaired mitochondrial activity and insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:2419–2421. author reply 2419-2421

    Article  PubMed  Google Scholar 

  • Moloney AM, Griffin RJ, Timmons S, O’Connor R, Ravid R, O’Neill C (2010) Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging 31:224–243

    Article  CAS  PubMed  Google Scholar 

  • Moran C, Sanz-Rodriguez A, Jimenez-Pacheco A, Martinez-Villareal J, McKiernan RC, Jimenez-Mateos EM et al (2013) Bmf upregulation through the AMP-activated protein kinase pathway may protect the brain from seizure-induced cell death. Cell Death Dis 4:e606

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ng CH, Guan MS, Koh C, Ouyang X, Yu F, Tan EK, O’Neill SP, Zhang X, Chung J, Lim KL (2012) AMP kinase activation mitigates dopaminergic dysfunction and mitochondrial abnormalities in Drosophila models of Parkinson’s disease. J Neurosci 32:14311–14317

    Article  CAS  PubMed  Google Scholar 

  • Nilsson LG, Nilsson E (2009) Overweight and cognition. Scand J Psychol 50:660–667

    Article  PubMed  Google Scholar 

  • Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461

    Article  PubMed  Google Scholar 

  • Pintana H, Apaijai N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2012) Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats. Life Sci 91:409–414

    Article  CAS  PubMed  Google Scholar 

  • Pipatpiboon N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2012) PPARgamma agonist improves neuronal insulin receptor function in hippocampus and brain mitochondria function in rats with insulin resistance induced by long term high-fat diets. Endocrinology 153:329–338

    Article  CAS  PubMed  Google Scholar 

  • Pipatpiboon N, Pintana H, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2013) DPP4-inhibitor improves neuronal insulin receptor function, brain mitochondrial function and cognitive function in rats with insulin resistance induced by high-fat diet consumption. Eur J Neurosci 37:839–849

    Article  PubMed  Google Scholar 

  • Potter WB, O’Riordan KJ, Barnett D, Osting SM, Wagoner M, Burger C, Roopra A (2010) Metabolic regulation of neuronal plasticity by the energy sensor AMPK. PLoS ONE 5:e8996

    Article  PubMed Central  PubMed  Google Scholar 

  • Prakash A, Shur B, Kumar A (2013) Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. Int J Neurosci 123:636–645

    Article  CAS  PubMed  Google Scholar 

  • Pratchayasakul W, Kerdphoo S, Petsophonsakul P, Pongchaidecha A, Chattipakorn N, Chattipakorn SC (2011) Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone. Life Sci 88:619–627

    Article  CAS  PubMed  Google Scholar 

  • Pu P, Gao DM, Mohamed S, Chen J, Zhang J, Zhou XY, Zhou NJ, Xie J, Jiang H (2012) Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Arch Biochem Biophys 518:61–70

    Article  CAS  PubMed  Google Scholar 

  • Rabol R, Boushel R, Dela F (2006) Mitochondrial oxidative function and type 2 diabetes. Appl Physiol Nutr Metab 31:675–683

    Article  PubMed  Google Scholar 

  • Rajadurai M, Prince PS (2007) Preventive effect of naringin on cardiac mitochondrial enzymes during isoproterenol-induced myocardial infarction in rats: a transmission electron microscopic study. J Biochem Mol Toxicol 21:354–361

    Article  CAS  PubMed  Google Scholar 

  • Ramesh E, Alshatwi AA (2013) Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol 51:97–105

    Article  CAS  PubMed  Google Scholar 

  • Reddy PH, Tripathi R, Troung Q, Tirumala K, Reddy TP, Anekonda V et al (2012) Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer’s disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta 1822:639–649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Saha AK, Xu XJ, Lawson E, Deoliveira R, Brandon AE, Kraegen EW, Ruderman NB (2010) Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes 59:2426–2434

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D et al (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci USA 101:3100–3105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schulingkamp RJ, Pagano TC, Hung D, Raffa RB (2000) Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 24:855–872

    Article  CAS  PubMed  Google Scholar 

  • Sellbom KS, Gunstad J (2012) Cognitive function and decline in obesity. J Alzheimers Dis 30(Suppl 2):S89–S95

    PubMed  Google Scholar 

  • Shin SM, Cho IJ, Kim SG (2009) Resveratrol protects mitochondria against oxidative stress through AMP-activated protein kinase-mediated glycogen synthase kinase-3beta inhibition downstream of poly(ADP-ribose)polymerase-LKB1 pathway. Mol Pharmacol 76:884–895

    Article  CAS  PubMed  Google Scholar 

  • Skeberdis VA, Lan J, Zheng X, Zukin RS, Bennett MV (2001) Insulin promotes rapid delivery of N-methyl-d-aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci USA 98:3561–3566

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK (1996) Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 26:167–181

    Article  CAS  PubMed  Google Scholar 

  • Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS, Egan JM, Mattson MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088

    Article  PubMed Central  PubMed  Google Scholar 

  • Taddeo EP, Laker RC, Breen DS, Akhtar YN, Kenwood BM, Liao JA et al (2014) Opening of the mitochondrial permeability transition pore links mitochondrial dysfunction to insulin resistance in skeletal muscle. Mol Metab 3:124–134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takamura A, Okamoto Y, Kawarabayashi T, Yokoseki T, Shibata M, Mouri A et al (2011) Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer’s disease model mouse. Mol Neurodegener 6:20

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • van der Heide LP, Kamal A, Artola A, Gispen WH, Ramakers GM (2005) Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. J Neurochem 94:1158–1166

    Article  PubMed  Google Scholar 

  • Wan Q, Xiong ZG, Man HY, Ackerley CA, Braunton J, Lu WY, Becker LE, MacDonald JF, Wang YT (1997) Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin. Nature 388:686–690

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Brautigan DL (2013) Alpha-SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKalpha in vitro. Nat Commun 4:1559

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang YT, Linden DJ (2000) Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25:635–647

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Gao K, Li X, Shen X, Zhang X, Ma C, Qin C, Zhang L (2012) Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer’s disease. Pharmacol Biochem Behav 102:13–20

    Article  CAS  PubMed  Google Scholar 

  • Wang DM, Yang YJ, Zhang L, Zhang X, Guan FF, Zhang LF (2013) Naringin enhances CaMKII activity and improves long-term memory in a mouse model of Alzheimer’s disease. Int J Mol Sci 14:5576–5586

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Warren BE, Lou PH, Lucchinetti E, Zhang L, Clanachan AS, Affolter A, Hersberger M, Zaugg M, Lemieux H (2014) Early mitochondrial dysfunction in glycolytic muscle, but not oxidative muscle, of the fructose-fed insulin-resistant rat. Am J Physiol Endocrinol Metab 306:E658–E667

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu XJ, Gauthier MS, Hess DT, Apovian CM, Cacicedo JM, Gokce N, Farb M, Valentine RJ, Ruderman NB (2012) Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue. J Lipid Res 53:792–801

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yano M, Watanabe K, Yamamoto T, Ikeda K, Senokuchi T, Lu M et al (2011) Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice. J Biol Chem 286:3992–4002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present work was supported by National Natural Science Foundation of China (U1304806 and U1304809), the China Scholarship Council (File No. 201408410296), and the Scientific Research Fund of Henan University of Science and Technology (NO. 09001664).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Statement

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were approved by the Animal Ethics Committee of Henan University of Science and Technology in China and in accordance with the ethical standards of the institution. Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

  1. Department of Pathogen Biology, Medical College, Henan University of Science and Technology, No.6, Anhui Road, Jianxi District, Luoyang, 471003, China

    Dongmei Wang, Wenlan Wu, Xiaoying Zhu & Yong Wang

  2. Department of Neurology, The First Affiliated Hospital of Henan University of Science and Technology, Jinghua Road 24, Luoyang, 471003, China

    Junqiang Yan

  3. Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Jingba Road 2, Zhengzhou, 450014, China

    Jing Chen

Authors
  1. Dongmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junqiang Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenlan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoying Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dongmei Wang.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

10571_2015_201_MOESM1_ESM.docx

Fig. S1. Swimming speed and path length in the probe test of Morris water maze. The swimming speed (A) and path length in the probe test (B) of mice on a control diet (CD) and treated with 100 mg/kg/day naringin (CDN), high-fat diet (HFD), high-fat diet and treated with 100 mg/kg/day naringin (HFDN) were tabulated. All data are presented as mean ± S.E.M. (n = 15). Supplementary material 1 (DOCX 355 kb)

10571_2015_201_MOESM2_ESM.docx

Fig. S2. Effects of naringin on food intake in HFD-induced obese mice. Food intake of mice during treatment was measured. All data are presented as mean ± S.E.M. (n = 15). Supplementary material 2 (DOCX 221 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, D., Yan, J., Chen, J. et al. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice. Cell Mol Neurobiol 35, 1061–1071 (2015). https://doi.org/10.1007/s10571-015-0201-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-015-0201-y

Keywords

Search

Navigation