Hypothalamic 5′-adenosine monophosphate-activated protein kinase (AMPK) senses intracellular metabolic stress, i.e., an increase in the cellular AMP:ATP ratio, and integrates diverse hormonal and nutritional signals to restore energy balance. Recent evidence suggests that different nutrients can modulate AMPK activity in the hypothalamus, thereby controlling weight gain through a leptin-independent mechanism. Understanding the mechanisms by which nutrients control hypothalamic AMPK activity is crucial to the development of effective nutritional interventions for the treatment of food intake-related disorders, such as anorexia and obesity. This article highlights the current evidence for the intricate relationship between nutrients and hypothalamic AMPK activity. © 2013 Elsevier Inc.622171178Flegal, K.M., Graubard, B.I., Williamson, D.F., Gail, M.H., Excess deaths associated with underweight, overweight, and obesity (2005) Journal of the American Medical Association, 293 (15), pp. 1861-1867. , DOI 10.1001/jama.293.15.1861Fearon, K., Strasser, F., Anker, S.D., Definition and classification of cancer cachexia: An international consensus (2011) Lancet Oncol, 12, pp. 489-495Pauling, L., Evolution and the need for ascorbic acid (1970) Proc Natl Acad Sci U S A, 67, pp. 1643-1648Cameron, E., Pauling, L., Ascorbic acid and the glycosaminoglycans. An orthomolecular approach to cancer and other diseases (1973) Oncology, 27, pp. 181-192Pauling, L., Alcantara, E.N., Speckmann, E.W., Diet, nutrition, and cancer (1977) American Journal of Clinical Nutrition, 30 (5), pp. 661-663A critique of low-carbohydrate ketogenic weight reduction regimens. A review of Dr. Atkins' diet revolution (1973) JAMA, 224, pp. 1415-1419Gardner, C.D., Kiazand, A., Alhassan, S., Kim, S., Stafford, R.S., Balise, R.R., Kraemer, H.C., King, A.C., Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: The A to Z weight loss study: A randomized trial (2007) Journal of the American Medical Association, 297 (9), pp. 969-977. , http://jama.ama-assn.org/cgi/reprint/297/9/969, DOI 10.1001/jama.297.9.969Schwartz, M.W., Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity (2001) Journal of Clinical Investigation, 108 (7), pp. 963-964. , DOI 10.1172/JCI200114127Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S., Schwartz, M.W., Central nervous system control of food intake and body weight (2006) Nature, 443 (7109), pp. 289-295. , DOI 10.1038/nature05026, PII NATURE05026Woods, A., Cheung, P.C., Smith, F.C., Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro (1996) J Biol Chem, 271, pp. 10282-10290Dhillo, W.S., Appetite regulation: An overview (2007) Thyroid, 17 (5), pp. 433-445. , DOI 10.1089/thy.2007.0018Ropelle, E.R., Pauli, J.R., Zecchin, K.G., Ueno, M., De Souza, C.T., Morari, J., Faria, M.C., Carvalheira, J.B.C., A central role for neuronal adenosine 5′-monophosphate-activated protein kinase in cancer-induced anorexia (2007) Endocrinology, 148 (11), pp. 5220-5229. , http://endo.endojournals.org/cgi/reprint/148/11/5220, DOI 10.1210/en.2007-0381Carvalheira, J.B.C., Ribeiro, E.B., Araujo, E.P., Guimaraes, R.B., Telles, M.M., Torsoni, M., Gontijo, J.A.R., Saad, M.J.A., Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats (2003) Diabetologia, 46 (12), pp. 1629-1640. , DOI 10.1007/s00125-003-1246-xRopelle, E.R., Fernandes, M.F., Flores, M.B., Central exercise action increases the AMPK and mTOR response to leptin (2008) PLoS One, 3, p. 3856Ropelle, E.R., Pauli, J.R., Fernandes, M.F., A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss (2008) Diabetes, 57, pp. 594-605Ropelle, E.R., Pauli, J.R., Prada, P., Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats (2009) J Physiol, 587, pp. 2341-2351Ropelle, E.R., Flores, M.B., Cintra, D.E., IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition (2010) PLoS Biol, 8, p. 1000465Pimentel, G.D., Lira, F.S., Rosa, J.C., Intake of trans fatty acids during gestation and lactation leads to hypothalamic inflammation via TLR4/NFkappaBp65 signaling in adult offspring (2012) J Nutr Biochem, 23, pp. 265-271Xue, B., Kahn, B.B., AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues (2006) Journal of Physiology, 574 (1), pp. 73-83. , DOI 10.1113/jphysiol.2006.113217Minokoshi, Y., Alquier, T., Furukawa, H., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Kahn, B.B., AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus (2004) Nature, 428 (6982), pp. 569-574. , DOI 10.1038/nature02440Kahn, B.B., Alquier, T., Carling, D., Hardie, D.G., AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism (2005) Cell Metabolism, 1 (1), pp. 15-25. , DOI 10.1016/j.cmet.2004.12.003, PII S1550413104000099Cota, D., Proulx, K., Blake Smith, K.A., Kozma, S.C., Thomas, G., Woods, S.C., Seeley, R.J., Hypothalamic mTOR signaling regulates food intake (2006) Science, 312 (5775), pp. 927-930. , DOI 10.1126/science.1124147Lage, R., Dieguez, C., Vidal-Puig, A., AMPK: A metabolic gauge regulating whole-body energy homeostasis (2008) Trends Mol Med, 14, pp. 539-549Kola, B., Hubina, E., Tucci, S.A., Kirkham, T.C., Garcia, E.A., Mitchell, S.E., Williams, L.M., Korbonits, M., Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase (2005) Journal of Biological Chemistry, 280 (26), pp. 25196-25201. , DOI 10.1074/jbc.C500175200Claret, M., Smith, M.A., Batterham, R.L., Selman, C., Choudhury, A.I., Fryer, L.G.D., Clements, M., Withers, D.J., AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons (2007) Journal of Clinical Investigation, 117 (8), pp. 2325-2336. , http://www.jci.org/cgi/reprint/117/8/2325, DOI 10.1172/JCI31516Lopez, M., Lage, R., Saha, A.K., Perez-Tilve, D., Vazquez, M.J., Varela, L., Sangiao-Alvarellos, S., Vidal-Puig, A., Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin (2008) Cell Metabolism, 7 (5), pp. 389-399. , DOI 10.1016/j.cmet.2008.03.006, PII S1550413108000776Lopez, M., Varela, L., Vazquez, M.J., Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance (2010) Nat Med, 16, pp. 1001-1008Claret, M., Smith, M.A., Knauf, C., Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice (2011) Diabetes, 60, pp. 735-745Carling, D., Hardie, D.G., The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase (1989) Biochimica et Biophysica Acta - Molecular Cell Research, 1012 (1), pp. 81-86. , DOI 10.1016/0167-4889(89)90014-1Beg, Z.H., Allmann, D.W., Gibson, D.M., Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol (1973) Biochem Biophys Res Commun, 54, pp. 1362-1369Carlson, C.A., Kim, K.H., Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation (1973) J Biol Chem, 248, pp. 378-380Hardie, D.G., The AMP-activated protein kinase pathway - New players upstream and downstream (2004) Journal of Cell Science, 117 (23), pp. 5479-5487. , DOI 10.1242/jcs.01540Minokoshi, Y., Kim, Y.-B., Peroni, O.D., Fryer, L.G.D., Muller, C., Carling, D., Kahn, B.B., Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase (2002) Nature, 415 (6869), pp. 339-343. , DOI 10.1038/415339aKubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Kadowaki, T., Adiponectin stimulates amp-activated protein kinase in the hypothalamus and increases food intake (2007) Cell Metabolism, 6 (1), pp. 55-68. , DOI 10.1016/j.cmet.2007.06.003, PII S1550413107001593Hayes, M.R., Bradley, L., Grill, H.J., Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling (2009) Endocrinology, 150, pp. 2654-2659Andersson, U., Filipsson, K., Abbott, C.R., Woods, A., Smith, K., Bloom, S.R., Carling, D., Small, C.J., AMP-activated Protein Kinase Plays a Role in the Control of Food Intake (2004) Journal of Biological Chemistry, 279 (13), pp. 12005-12008. , DOI 10.1074/jbc.C300557200Obici, S., Feng, Z., Arduini, A., Conti, R., Rossetti, L., Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production (2003) Nature Medicine, 9 (6), pp. 756-761. , DOI 10.1038/nm873Loftus, T.M., Jaworsky, D.E., Frehywot, C.L., Townsend, C.A., Ronnett, G.V., Daniel Lane, M., Kuhajda, F.P., Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors (2000) Science, 288 (5475), pp. 2379-2381. , DOI 10.1126/science.288.5475.2379Blouet, C., Jo, Y.H., Li, X., Schwartz, G.J., Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit (2009) J Neurosci, 29, pp. 8302-8311Chau-Van, C., Gamba, M., Salvi, R., Gaillard, R.C., Pralong, F.P., Metformin inhibits adenosine 5′-monophosphate-activated kinase activation and prevents increases in neuropeptide Y expression in cultured hypothalamic neurons (2007) Endocrinology, 148 (2), pp. 507-511. , http://endo.endojournals.org/cgi/reprint/148/2/507, DOI 10.1210/en.2006-1237Kim, Y.W., Kim, J.Y., Park, Y.H., Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance (2006) Diabetes, 55, pp. 716-724Dansinger, M.L., Gleason, J.A., Griffith, J.L., Selker, H.P., Schaefer, E.J., Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for weight loss and heart disease risk reduction: A randomized trial (2005) Journal of the American Medical Association, 293 (1), pp. 43-53. , DOI 10.1001/jama.293.1.43Shigemitsu, K., Tsujishita, Y., Miyake, H., Hidayat, S., Tanaka, N., Hara, K., Yonezawa, K., Structural requirement of leucine for activation of p70 S6 kinase (1999) FEBS Letters, 447 (2-3), pp. 303-306. , DOI 10.1016/S0014-5793(99)00304-X, PII S001457939900304XTome, D., Schwarz, J., Darcel, N., Protein, amino acids, vagus nerve signaling, and the brain (2009) Am J Clin Nutr, 90, pp. 838S-843SPurpera, M.N., Shen, L., Taghavi, M., Impaired branched chain amino acid metabolism alters feeding behavior and increases orexigenic neuropeptide expression in the hypothalamus (2012) J Endocrinol, 212, pp. 85-94Catania, C., Binder, E., Cota, D., MTORC1 signaling in energy balance and metabolic disease (2011) Int J Obes (Lond), 35, pp. 751-761Cota, D., Matter, E.K., Woods, S.C., The role of hypothalamic mammalian target of rapamycin complex 1 signaling in diet-induced obesity (2008) J Neurosci, 28, pp. 7202-7208Xu, G., Kwon, G., Cruz, W.S., Marshall, C.A., McDaniel, M.L., Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic β-cells (2001) Diabetes, 50 (2), pp. 353-360Fujita, S., Dreyer, H.C., Drummond, M.J., Glynn, E.L., Cadenas, J.G., Yoshizawa, F., Volpi, E., Rasmussen, B.B., Nutrient signalling in the regulation of human muscle protein synthesis (2007) Journal of Physiology, 582 (2), pp. 813-823. , DOI 10.1113/jphysiol.2007.134593Wilson, G.J., Layman, D.K., Moulton, C.J., Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats (2011) Am J Physiol Endocrinol Metab, 301, pp. 1236-E1242Du, M., Shen, Q.W., Zhu, M.J., Ford, S.P., Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase (2007) Journal of Animal Science, 85 (4), pp. 919-927. , DOI 10.2527/jas.2006-342Aftring, R.P., Block, K.P., Buse, M.G., Leucine and isoleucine activate skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo (1986) Am J Physiol, 250, pp. 599-E604Mayer, J., Regulation of energy intake and the body weight: The glucostatic theory and the lipostatic hypothesis (1955) Ann N y Acad Sci, 63, pp. 15-43Anand, B.K., Chhina, G.S., Sharma, K.N., Activity of single neurons in the hypothalamic feeding centers: Effect of glucose (1964) Am J Physiol, 207, pp. 1146-1154Oomura, Y., Kimura, K., Ooyama, H., Reciprocal activities of the ventromedial and lateral hypothalamic areas of cats (1964) Science, 143, pp. 484-485Mizuno, Y., Oomura, Y., Glucose responding neurons in the nucleus tractus solitarius of the rat: In vitro study (1984) Brain Research, 307 (1-2), pp. 109-116Nakano, Y., Oomura, Y., Lenard, L., Feeding-related activity of glucose- and morphine-sensitive neurons in the monkey amygdala (1986) Brain Research, 399 (1), pp. 167-172. , DOI 10.1016/0006-8993(86)90613-XCha, S.H., Wolfgang, M., Tokutake, Y., Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake (2008) Proc Natl Acad Sci U S A, 105, pp. 16871-16875Kim, M.-S., Park, J.-Y., Namkoong, C., Jang, P.-G., Ryu, J.-W., Song, H.-S., Yun, J.-Y., Lee, K.-U., Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase (2004) Nature Medicine, 10 (7), pp. 727-733. , DOI 10.1038/nm1061Wolfgang, M.J., Cha, S.H., Sidhaye, A., Regulation of hypothalamic malonyl-CoA by central glucose and leptin (2007) Proc Natl Acad Sci U S A, 104, pp. 19285-19290Lee, K., Li, B., Xi, X., Suh, Y., Martin, R.J., Role of neuronal energy status in the regulation of adenosine 5′-monophosphate-activated protein kinase, orexigenic neuropeptides expression, and feeding behavior (2005) Endocrinology, 146 (1), pp. 3-10. , DOI 10.1210/en.2004-0968Cai, F., Gyulkhandanyan, A.V., Wheeler, M.B., Belsham, D.D., Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: Additive effects of leptin or insulin (2007) Journal of Endocrinology, 192 (3), pp. 605-614. , DOI 10.1677/JOE-06-0080Zhang, H., Zhang, G., Gonzalez, F.J., Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation (2011) PLoS Biol, 9, p. 1001112De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J.A., Velloso, L.A., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus (2005) Endocrinology, 146 (10), pp. 4192-4199. , http://endo.endojournals.org/cgi/reprint/146/10/4192, DOI 10.1210/en.2004-1520Zhang, X., Zhang, G., Zhang, H., Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity (2008) Cell, 135, pp. 61-73Posey, K.A., Clegg, D.J., Printz, R.L., Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet (2009) Am J Physiol Endocrinol Metab, 296, pp. 1003-E1012Benoit, S.C., Kemp, C.J., Elias, C.F., Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents (2009) J Clin Invest, 119, pp. 2577-2589Tsukumo, D.M.L., Carvalho-Filho, M.A., Carvalheira, J.B.C., Prada, P.O., Hirabara, S.M., Schenka, A.A., Araujo, E.P., Saad, M.J.A., Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance (2007) Diabetes, 56 (8), pp. 1986-1998. , http://diabetes.diabetesjournals.org/cgi/reprint/56/8/1986, DOI 10.2337/db06-1595Lumeng, C.N., Saltiel, A.R., Inflammatory links between obesity and metabolic disease (2011) J Clin Invest, 121, pp. 2111-2117Watts, C., Location, location, location: Identifying the neighborhoods of LPS signaling (2008) Nature Immunology, 9 (4), pp. 343-345. , DOI 10.1038/ni0408-343, PII NI0408-343Horng, T., Barton, G.M., Medzhitov, R., TIRAP: An adapter molecule in the Toll signaling pathway (2001) Nat Immunol, 2, pp. 835-841Martin, T.L., Alquier, T., Asakura, K., Furukawa, N., Preitner, F., Kahn, B.B., Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle (2006) Journal of Biological Chemistry, 281 (28), pp. 18933-18941. , http://www.jbc.org/cgi/reprint/281/28/18933, DOI 10.1074/jbc.M512831200Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., Rossetti, L., Central administration of oleic acid inhibits glucose production and food intake (2002) Diabetes, 51 (2), pp. 271-275Jo, Y.H., Su, Y., Gutierrez-Juarez, R., Oleic acid directly regulates POMC neuron excitability in the hypothalamus (2009) J Neurophysiol, 101, pp. 2305-2316Schwinkendorf, D.R., Tsatsos, N.G., Gosnell, B.A., Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism (2011) Int J Obes (Lond), 35, pp. 336-344Jia, M., Xue, N., Cao, Z., Effects of dietary different ratios of n-3 to n-6 polyunsaturated fatty acids influence lipid metabolism and appetite of rats (2009) Wei Sheng Yan Jiu, 38, pp. 175-178Gomez-Pinilla, F., Ying, Z., Differential effects of exercise and dietary docosahexaenoic acid on molecular systems associated with control of allostasis in the hypothalamus and hippocampus (2010) Neuroscience, 168, pp. 130-137Wallace, R.J., McKain, N., Shingfield, K.J., Devillard, E., Isomers of conjugated linoleic acids are synthesized via different mechanisms in ruminal digesta and bacteria (2007) Journal of Lipid Research, 48 (10), pp. 2247-2254. , http://www.jlr.org/cgi/reprint/48/10/2247, DOI 10.1194/jlr.M700271-JLR200Pariza, M.W., Park, Y., Cook, M.E., The biologically active isomers of conjugated linoleic acid (2001) Progress in Lipid Research, 40 (4), pp. 283-298. , DOI 10.1016/S0163-7827(01)00008-X, PII S016378270100008XPariza, M.W., Perspective on the safety and effectiveness of conjugated linoleic acid (2004) Am J Clin Nutr, 79, pp. 1132S-1136SJiang, S., Wang, Z., Riethoven, J.J., Conjugated linoleic acid activates AMP-activated protein kinase and reduces adiposity more effectively when used with metformin in mice (2009) J Nutr, 139, pp. 2244-2251Miner, J.L., Cederberg, C.A., Nielsen, M.K., Chen, X., Baile, C.A., Conjugated linoleic acid (CLA), body fat, and apoptosis (2001) Obesity Research, 9 (2), pp. 129-134Park, Y., Storkson, J.M., Albright, K.J., Liu, W., Pariza, M.W., Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice (1999) Lipids, 34 (3), pp. 235-241Cao, Z.-P., Wang, F., Xiang, X.-S., Cao, R., Zhang, W.-B., Gao, S.-B., Intracerebroventricular administration of conjugated linoleic acid (CLA) inhibits food intake by decreasing gene expression of NPY and AgRP (2007) Neuroscience Letters, 418 (3), pp. 217-221. , DOI 10.1016/j.neulet.2007.03.010, PII S0304394007002947So, M.H., Tse, I.M., Li, E.T., Dietary fat concentration influences the effects of trans-10, cis-12 conjugated linoleic acid on temporal patterns of energy intake and hypothalamic expression of appetite-controlling genes in mice (2009) J Nutr, 139, pp. 145-151Carreau, J.P., Biosynthesis of lipoic acid via unsaturated fatty acids (1979) Methods Enzymol, 62, pp. 152-158Reed, L.J., A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes (2001) J Biol Chem, 276, pp. 38329-38336Liu, J., The effects and mechanisms of mitochondrial nutrient α-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: An overview (2008) Neurochemical Research, 33 (1), pp. 194-203. , DOI 10.1007/s11064-007-9403-0El Midaoui, A., Elimadi, A., Wu, L., Haddad, P.S., De Champlain, J., Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production (2003) American Journal of Hypertension, 16 (3), pp. 173-179. , DOI 10.1016/S0895-7061(02)03253-3, PII S0895706102032533Targonsky, E.D., Dai, F., Koshkin, V., Karaman, G.T., Gyulkhandanyan, A.V., Zhang, Y., Chan, C.B., Wheeler, M.B., Lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells (2006) Diabetologia, 49 (7), pp. 1587-1598. , DOI 10.1007/s00125-006-0265-9Zhang, Y., Han, P., Wu, N., Amelioration of lipid abnormalities by alpha-lipoic acid through antioxidative and anti-inflammatory effects (2011) Obesity (Silver Spring), 19, pp. 1647-1653Turnley, A.M., Stapleton, D., Mann, R.J., Witters, L.A., Kemp, B.E., Bartlett, P.F., Cellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system (1999) Journal of Neurochemistry, 72 (4), pp. 1707-1716. , DOI 10.1046/j.1471-4159.1999.721707.xCheng, P.Y., Lee, Y.M., Yen, M.H., Reciprocal effects of alpha-lipoic acid on adenosine monophosphate- activated protein kinase activity in obesity induced by ovariectomy in rats (2011) Menopause, 18, pp. 1010-1017Zhou, J., Zhou, S., Tang, J., Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats (2009) Eur J Pharmacol, 606, pp. 262-268Hur, J.M., Hyun, M.S., Lim, S.Y., The combination of berberine and irradiation enhances anti-cancer effects via activation of p38 MAPK pathway and ROS generation in human hepatoma cells (2009) J Cell Biochem, 107, pp. 955-964Wang, J.M., Yang, Z., Xu, M.G., Berberine-induced decline in circulating CD31 +/CD42- microparticles is associated with improvement of endothelial function in humans (2009) Eur J Pharmacol, 614, pp. 77-83Wang, X., Wang, R., Xing, D., Su, H., Ding, Y., Du, L., Kinetic difference of berberine between hippocampus and plasma in rat after intravenous administration of Coptidis rhizoma extract (2005) Life Sciences, 77 (24), pp. 3058-3067. , DOI 10.1016/j.lfs.2005.02.033, PII S0024320505005886Brusq, J.-M., Ancellin, N., Grondin, P., Guillard, R., Martin, S., Saintillan, Y., Issandou, M., Inhibition of lipid synthesis through activation of AMP kinase: An additional mechanism for the hypolipidemic effects of berberine (2006) Journal of Lipid Research, 47 (6), pp. 1281-1288. , http://www.jlr.org/cgi/reprint/47/6/1281, DOI 10.1194/jlr.M600020-JLR200Yin, J., Gao, Z., Liu, D., Berberine improves glucose metabolism through induction of glycolysis (2008) Am J Physiol Endocrinol Metab, 294, pp. 148-E156Kim, W.S., Lee, Y.S., Cha, S.H., Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity (2009) Am J Physiol Endocrinol Metab, 296, pp. 812-E819