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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Electroacupuncture inhibits weight gain in diet-induced obese rats by activating hypothalamicLKB1-AMPK signaling

Authors: Jing Xu, Liang Chen, Lewei Tang, Le Chang, Si Liu, Jinfeng Tan, Yinglong Chen, Yulan Ren, Fanrong Liang, Jin Cui

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

Electroacupuncture (EA) is reported to be an effective treatment for obesity, but its mechanism is unclear. This study aimed to investigate the relationship between hypothalamic LKB1-AMPK-ACC signaling and EA.

Methods

Fifty male Sprague–Dawley rats were divided into two groups fed either chow (chow-fed group) or high-fat diet (HF group). After 4 weeks of feeding, obese rats in the HF group (defined as weighing 20 % or more than rats in the chow-fed group) were randomly allocated into an EA or Diet-induced obesity (DIO) group. The EA group was given EA on bilateral ST25–ST36 for 4 weeks, while the DIO group received no further intervention. Body weight of the chow-fed, DIO, and EA groups were measured weekly. mRNA and protein levels of the hypothalamic LKB1-AMPK-ACC signaling pathway were detected using real-time (RT)-PCR and western blot, respectively.

Results

After 4 weeks of EA treatment, the weight growth trend of rats in the EA group was inhibited compared with those in the DIO group. RT-PCR and western blotting showed that EA upregulated the transcription of Adenosine 5′-monophosphate -activated protein kinase α2 (AMPKα2), promoted protein expression of Liver kinase B1 (LKB1) and AMPKα1, and inhibited acetyl-CoA carboxylase (ACC) protein expression in the hypothalamus.

Conclusions

This study suggests that hypothalamic LKB1-AMPK-ACC signaling plays an important role in EA treatment for obesity.
Literature
1.
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 Suppl 2):S102–38.CrossRefPubMed
2.
Finkelstein EA, Kruger E. Meta- and cost-effectiveness analysis of commercial weight loss strategies. Obesity. 2014;22(9):1942–51.CrossRefPubMed
3.
Belivani M, Dimitroula C, Katsiki N, Apostolopoulou M, Cummings M, Hatzitolios AI. Acupuncture in the treatment of obesity: a narrative review of the literature. Acupunct Med. 2013;31(1):88–97.CrossRefPubMed
4.
Sui Y, Zhao HL, Wong VC, Brown N, Li XL, Kwan AK, et al. A systematic review on use of Chinese medicine and acupuncture for treatment of obesity. Obes Rev. 2012;13(5):409–30.CrossRefPubMed
5.
Tian N, Wang F, Tian DR, Zou Y, Wang SW, Guan LL, et al. Electroacupuncture suppresses expression of gastric ghrelin and hypothalamic NPY in chronic food restricted rats. Peptides. 2006;27(9):2313–20.CrossRefPubMed
6.
Gong M, Wang X, Mao Z, Shao Q, Xiang X, Xu B. Effect of electroacupuncture on leptin resistance in rats with diet-induced obesity. Am J Chin Med. 2012;40(3):511–20.CrossRefPubMed
7.
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13(4):251–62.CrossRefPubMed
8.
Blanco Martinez de Morentin P, Gonzalez CR, Saha AK, Martins L, Dieguez C, Vidal-Puig A, et al. Hypothalamic AMP-activated protein kinase as a mediator of whole body energy balance. Rev Endocr Metab Disord. 2011;12(3):127–40.CrossRefPubMed
9.
Carling D, Sanders MJ, Woods A. The regulation of AMP-activated protein kinase by upstream kinases. Int J Obes (Lond). 2008;32 Suppl 4:S55–9.CrossRef
10.
Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol. 2003;13(22):2004–8.CrossRefPubMed
11.
Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004;101(10):3329–35.CrossRefPubMedPubMedCentral
12.
Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310(5754):1642–6.CrossRefPubMedPubMedCentral
13.
Sakamoto K, McCarthy A, Smith D, Green KA, Grahame Hardie D, Ashworth A, et al. Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. 2005;24(10):1810–20.CrossRefPubMedPubMedCentral
14.
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108(8):1167–74.CrossRefPubMedPubMedCentral
15.
Lopez M, Lage R, Saha AK, Perez-Tilve D, Vazquez MJ, Varela L, et al. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab. 2008;7(5):389–99.CrossRefPubMed
16.
Abu-Elheiga L, Matzuk MM, Abo-Hashema KA, Wakil SJ. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science. 2001;291(5513):2613–6.CrossRefPubMed
17.
Savage DB, Choi CS, Samuel VT, Liu ZX, Zhang D, Wang A, et al. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest. 2006;116(3):817–24.CrossRefPubMedPubMedCentral
18.
Tominaga A, Ishizaki N, Naruse Y, Kitakoji H, Yamamura Y. Repeated application of low-frequency electroacupuncture improves high-fructose diet-induced insulin resistance in rats. Acupunct Med. 2011;29(4):276–83.CrossRefPubMed
19.
Kim SK, Sun B, Yoon H, Lee JH, Lee G, Sohn SH, et al. Expression levels of the hypothalamic AMPK gene determines the responsiveness of the rats to electroacupuncture-induced analgesia. BMC Complement Altern Med. 2014;14(1):211.CrossRefPubMedPubMedCentral
20.
Yu SG, Guo Y. Experimental Acupuncturology. Shanghai: Shanghai Science and Technology Press; 2009. p. 150–2.
21.
22.
Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, et al. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem. 2004;279(13):12005–8.CrossRefPubMed
23.
Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428(6982):569–74.CrossRefPubMed
24.
Wilkes JJ, Nguyen MT, Bandyopadhyay GK, Nelson E, Olefsky JM. Topiramate treatment causes skeletal muscle insulin sensitization and increased Acrp30 secretion in high-fat-fed male Wistar rats. Am J Physiol Endocrinol Metab. 2005;289(6):E1015–22.CrossRefPubMed
25.
Lessard SJ, Chen ZP, Watt MJ, Hashem M, Reid JJ, Febbraio MA, et al. Chronic rosiglitazone treatment restores AMPKalpha2 activity in insulin-resistant rat skeletal muscle. Am J Physiol Endocrinol Metab. 2006;290(2):E251–7.CrossRefPubMed
26.
Liu Y, Wan Q, Guan Q, Gao L, Zhao J. High-fat diet feeding impairs both the expression and activity of AMPKa in rats’ skeletal muscle. Biochem Biophys Res Commun. 2006;339(2):701–7.CrossRefPubMed
27.
Martin TL, Alquier T, Asakura K, Furukawa N, Preitner F, Kahn BB. Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle. J Biol Chem. 2006;281(28):18933–41.CrossRefPubMed
28.
Yu X, McCorkle S, Wang M, Lee Y, Li J, Saha AK, et al. Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia. 2004;47(11):2012–21.CrossRefPubMed
29.
Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, et al. AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun. 2004;320(2):449–54.CrossRefPubMed
30.
Viollet B, Horman S, Leclerc J, Lantier L, Foretz M, Billaud M, et al. AMPK inhibition in health and disease. Crit Rev Biochem Mol Biol. 2010;45(4):276–95.CrossRefPubMedPubMedCentral
31.
Villena JA, Viollet B, Andreelli F, Kahn A, Vaulont S, Sul HS. Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit. Diabetes. 2004;53(9):2242–9.CrossRefPubMed
32.
33.
Gao S, Kinzig KP, Aja S, Scott KA, Keung W, Kelly S, et al. Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci U S A. 2007;104(44):17358–63.CrossRefPubMedPubMedCentral
34.
Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, Kahn BB. p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin’s effect on food intake. Cell Metab. 2012;16(1):104–12.CrossRefPubMedPubMedCentral
35.
Zhang L, Li MM, Corcoran M, Zhang S, Cooper GJ. Essential roles of insulin, AMPK signaling and lysyl and prolyl hydroxylases in the biosynthesis and multimerization of adiponectin. Mol Cell Endocrinol. 2015;399:164–77.CrossRefPubMed
36.
Than A, Zhang X, Leow MK, Poh CL, Chong SK, Chen P. Apelin attenuates oxidative stress in human adipocytes. J Biol Chem. 2014;289(6):3763–74.CrossRefPubMed
37.
Barnes BR, Marklund S, Steiler TL, Walter M, Hjalm G, Amarger V, et al. The 5′-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle. J Biol Chem. 2004;279(37):38441–7.CrossRefPubMed
38.
Bergeron R, Previs SF, Cline GW, Perret P, Russell 3rd RR, Young LH, et al. Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes. 2001;50(5):1076–82.CrossRefPubMed
39.
Chen MB, McAinch AJ, Macaulay SL, Castelli LA, O’Brien PE, Dixon JB, et al. Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics. J Clin Endocrinol Metab. 2005;90(6):3665–72.CrossRefPubMed
40.
Cuthbertson DJ, Babraj JA, Mustard KJ, Towler MC, Green KA, Wackerhage H, et al. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 2007;56(8):2078–84.CrossRefPubMed
41.
Koistinen HA, Galuska D, Chibalin AV, Yang J, Zierath JR, Holman GD, et al. 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes. Diabetes. 2003;52(5):1066–72.CrossRefPubMed
42.
Steinberg GR, Smith AC, Van Denderen BJ, Chen Z, Murthy S, Campbell DJ, et al. AMP-activated protein kinase is not down-regulated in human skeletal muscle of obese females. J Clin Endocrinol Metab. 2004;89(9):4575–80.CrossRefPubMed
43.
Steinberg GR, McAinch AJ, Chen MB, O’Brien PE, Dixon JB, Cameron-Smith D, et al. The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab. 2006;91(9):3592–7.CrossRefPubMed
44.
Hardie DG. AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol. 2015;33:1–7.CrossRefPubMed
45.
Suter M, Riek U, Tuerk R, Schlattner U, Wallimann T, Neumann D. Dissecting the role of 5′-AMP for allosteric stimulation, activation, and deactivation of AMP-activated protein kinase. J Biol Chem. 2006;281(43):32207–16.CrossRefPubMed
46.
47.
Wang F, Tian DR, Han JS. Electroacupuncture in the treatment of obesity. Neurochem Res. 2008;33(10):2023–7.CrossRefPubMed
48.
Rolfe DF, Newman JM, Buckingham JA, Clark MG, Brand MD. Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR. Am J Physiol. 1999;276(3 Pt 1):C692–9.PubMed
49.
Divakaruni AS, Brand MD. The regulation and physiology of mitochondrial proton leak. Physiology. 2011;26(3):192–205.CrossRefPubMed
50.
Harper ME, Green K, Brand MD. The efficiency of cellular energy transduction and its implications for obesity. Annu Rev Nutr. 2008;28:13–33.CrossRefPubMed
51.
Villena JA. New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J. 2015;282(4):647–72.CrossRefPubMed
52.
Nikolic N, Rhedin M, Rustan AC, Storlien L, Thoresen GH, Stromstedt M. Overexpression of PGC-1alpha increases fatty acid oxidative capacity of human skeletal muscle cells. Biochem Res Int. 2012;2012:714074.CrossRefPubMed
53.
Liang F, Chen R, Nakagawa A, Nishizawa M, Tsuda S, Wang H, et al. Low-frequency electroacupuncture improves insulin sensitivity in obese diabetic mice through activation of SIRT1/PGC-1alpha in skeletal muscle. Evid Based Complement Alternat Med. 2011;2011:735297.CrossRefPubMed
54.
Du H, Zhou C, Wu H, Shan T, Wu Z, Xu B, et al. Effects of electroacupuncture on PGC-1 alpha expression in brown adipose tissue. Evid Based Complement Alternat Med. 2013;2013:625104.PubMedPubMedCentral
55.
Shen W, Wang Y, Lu SF, Hong H, Fu S, He S, et al. Acupuncture promotes white adipose tissue browning by inducing UCP1 expression on DIO mice. BMC Complement Altern Med. 2014;14(1):501.CrossRefPubMedPubMedCentral
56.
Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta. 2011;1813(7):1269–78.CrossRefPubMed
57.
Liu J, Jin H, Foreman RD, Lei Y, Xu X, Li S, et al. Chronic electrical stimulation at acupoints reduces body weight and improves blood glucose in obese rats via autonomic pathway. Obes Surg. 2014. [Epub ahead of print].
58.
Sun Y, Chen JD. Intestinal electric stimulation accelerates whole gut transit and promotes fat excrement in conscious rats. Int J Obes (Lond). 2009;33(8):817–23.CrossRef
59.
Tanner JM, Kearns DT, Kim BJ, Sloan C, Jia Z, Yang T, et al. Fasting-induced reductions in cardiovascular and metabolic variables occur sooner in obese versus lean mice. Exp Biol Med (Maywood, NJ). 2010;235(12):1489–97.CrossRef
60.
Sun Q, Xu Y. Simple obesity and obesity hyperlipemia treated with otoacupoint pellet pressure and body acupuncture. J Tradit Chin Med. 1993;13(1):22–6.PubMed
61.
Baocun Y, Caixia Z, Jing Y, Changle C, Shumin D. Observation and mechanism exploration of acupuncture on body weight reduction. J Tradit Chin Med. 2006;26(4):250–3.
62.
Cho SH, Lee JS, Thabane L, Lee J. Acupuncture for obesity: a systematic review and meta-analysis. Int J Obes (Lond). 2009;33(2):183–96.CrossRef
63.
Ji T, Li X, Lin L, Jiang L, Wang M, Zhou X, et al. An alternative to current therapies of functional dyspepsia: self-administrated transcutaneous electroacupuncture improves dyspeptic symptoms. Evid Based Complement Alternat Med. 2014;2014:832523.PubMedPubMedCentral
64.
Yu Z, Xia Y, Ju C, Shao Q, Mao Z, Gu Y, et al. Electroacupuncture regulates glucose-inhibited neurons in treatment of simple obesity. Neural Regen Res. 2013;8(9):809–16.PubMedPubMedCentral
65.
Ji B, Hu J, Ma S. Effects of electroacupuncture Zusanli (ST36) on food intake and expression of POMC and TRPV1 through afferents-medulla pathway in obese prone rats. Peptides. 2013;40:188–94.CrossRefPubMed
66.
Fei W, de Tian R, Tso P, Han JS. Arcuate nucleus of hypothalamus is involved in mediating the satiety effect of electroacupuncture in obese rats. Peptides. 2011;32(12):2394–9.CrossRef
67.
Kim SK, Bae H, Lee G, Jeong H, Woo HS, Han JB, et al. The endogenous CCK mediation of electroacupuncture stimulation-induced satiety in rats. Peptides. 2008;29(4):564–70.CrossRefPubMed
68.
Gucel F, Bahar B, Demirtas C, Mit S, Cevik C. Influence of acupuncture on leptin, ghrelin, insulin and cholecystokinin in obese women: a randomised, sham-controlled preliminary trial. Acupunct Med. 2012;30(3):203–7.CrossRefPubMed
69.
Kim SK, Kim J, Woo HS, Jeong H, Lee H, Min BI, et al. Electroacupuncture induces Fos expression in the nucleus tractus solitarius via cholecystokinin A receptor signaling in rats. Neurol Res. 2010;32 Suppl 1:116–9.CrossRefPubMed
Metadata
Title
Electroacupuncture inhibits weight gain in diet-induced obese rats by activating hypothalamicLKB1-AMPK signaling
Authors
Jing Xu
Liang Chen
Lewei Tang
Le Chang
Si Liu
Jinfeng Tan
Yinglong Chen
Yulan Ren
Fanrong Liang
Jin Cui
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0667-7

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