The contribution of hypothalamic histamine neurons to the central regulation of peripheral lipid metabolism was investigated in rats using in vivo microdialysis system. A bolus infusion of l-histamine at doses of 10–103 nmol/rat into the third cerebral ventricle (i3vt) dose-dependently increased glycerol concentration in the perfusate from the epididymal adipose tissue. I3vt infusion of 102 nmol/rat thioperamide, an autoinhibitory H3 receptor antagonist that activates histamine neurons to increase synthesis and release of neuronal histamine, convincingly mimicked histamine action in the augmented lipolysis. Intraperitoneal pretreatment with propranolol, a β-adrenoceptor antagonist, abolished the thioperamide-induced lipolytic action. An electrophysiological study demonstrated that efferent sympathetic nerves innervating the epididymal fat were activated after the i3vt infusion of thioperamide. Hypothalamic histamine neurons thus regulate peripheral lipid metabolism through the accelerating lipolytic action by activation of sympathetic β-adrenoceptor.
NilssonNO, StralforsP, FredriksonG, BelfrageP.Regulation of adipose tissue lipolysis: effects of noradrenaline and insulin on phosphorylation of hormone-sensitive lipase and on lipolysis in intact rat adipocytes. FEBS Lett111: 125–130, 1980.
2.
BamshadM, AokiVT, AdkisonMG, WarrenWS, BartnessTJ. Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am J Physiol275: R291–R299, 1998.
3.
GarofaloMA, KettelhutIC, RoselinoJES, MiglioriniRH. Effect of acute cold exposure on norepinephrine turnover rates in rat white adipose tissue. J Auton Nerv Syst60: 206–208, 1996.
4.
NiijimaA.Nervous regulation of metabolism. Prog Neurobiol33: 135–147, 1989.
5.
BarkaiA, AllweisC.Effect of electrical stimulation of the hypothalamus on plasma levels of free fatty acids and glucose in rats. Metabolism21: 921–927, 1972.
6.
TakahashiA, ShimazuT.Hypothalamic regulation of lipid metabolism in the rat: effect of hypothalamic stimulation on lipolysis. J Auton Nerv Syst4: 195–205, 1981.
7.
OokumaK, YoshimatsuH, SakataT, FujimotoK, FukagawaK.Hypothalamic sites of neuronal histamine action on food intake by rats. Brain Res490: 268–275, 1989.
8.
SakataT, FukagawaK, FujimotoK, YoshimatsuH, ShiraishiT, WadaH.Feeding induced by blockade of histamine H1-receptor in rat brain. Experientia44: 216–218, 1988.
9.
SakataT, OokumaK, FukagawaK, FujimotoK, YoshimatsuH, ShiraishiT, WadaH.Blockade of the histamine H1-receptor in the rat ventromedial hypothalamus and feeding elicitation. Brain Res441: 403–407, 1988.
10.
NishiboriM, ItohY, OishiR, SaekiK.Mechanism of the central hyperglycemic action of histamine in mice. J Pharmacol Exp Ther241: 582–586, 1987.
11.
YoshimatsuH, MachidoriH, DoiT, KurokawaM, OokumaK, KangM, FujimotoK, SakataT.Abnormalities in obese Zuckers: defective control of histaminergic functions. Physiol Behav54: 487–491, 1993.
12.
KniggeU, MatzenS, WarbergJ.Histamine as a neuroendocrine regulator of the stress-induced release of peripheral catecholamines. Endocrinology126: 1430–1434, 1990.
YoshimatsuH, ItateyamaE, KondouS, TajimaD, HimenoK, HidakaS, KurokawaM, SakataT.Hypothalamic neuronal histamine as a target of leptin in feeding behavior. Diabetes48: 2286–2291, 1999.
17.
MasakiT, YoshimatsuH, ChibaS, WatanabeT, SakataT.Targeted disruption of histamine H1 receptor attenuates regulatory effects of leptin on feeding, adiposity and UCP family in mice. Diabetes50: 385–391, 2001.
18.
DunbarJC, HuY, LuH.Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes46: 2040–2043, 1997.
19.
HwaJJ, GhibaudiL, ComptonD, FawziAB, StraderCD. Intracerebroventricular injection of leptin increases thermogenesis and mobilizes fat metabolism in ob/ob mice. Horm Met Res28: 659–663, 1996.
20.
SatohN, OgawaY, KatsuuraG, NumataY, MasuzakiH, YoshimasaY, NakaoK.Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system. Neurosci Lett249: 107–110, 1998.
21.
CusinI, ZakrzewskaKE, BossO, MuzzinP, GiacobinoJP, RicquierD, JeanrenaudB, JeanrenaudFR. Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. Diabetes47: 1014–1019, 1998.
22.
MasakiT, YoshimatsuH, ChibaS, WatanabeT, SakataT.Central infusion of histamine reduces fat accumulation and up-regulates UCP family in leptin-resistant obese mice. Diabetes50: 376–384, 2001.
23.
YoshimatsuH, HidakaS, NiijimaA, SakataT.Histamine neurons down-regulate ob gene expression in rat white adipose tissue. Inf Res50:(Suppl 2):72–73, 2001.
24.
SchwartzMW, WoodsSC, PorteDJr., SeeleyRJ, BaskinDG. Central nervous system control of food Intake. Nature404: 661–671, 2000.
25.
KalraSP, DubeMG, ShuyePU, BinXU, HorvathTL, KalraPS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrine Rev20: 68–100, 1999.
26.
InuiA.Transgenic approach to the study of body weight regulation. Pharmacol Rev52: 35–61, 2000.
27.
SakataT, TsutsuiK, FukushimaM, AraseK, KitaH, OomuraY.Feeding and hyperglycemia induced by 1.5-anhydroglucitol in the rat. Physiol Behav27: 401–405, 1981.
28.
ArnerP, BolinderJ, EliassonA, LundinA, UngerstedtU.Microdialysis of adipose tissue and blood for in vivo lipolysis studies. Am J Physiol255: E737–742, 1988.
29.
TossmanU, UngerstedtU.Microdialysis in the study of extracellular levels of amino acids in the rat brain. Acta Physiol Scand128: 9–14, 1986.
30.
BjorkhemI, ArnerP, ThoreA, OstmanJ.Sensitive kinetic bioluminescent assay of glycerol release from human fat cells. J Lipid Res22: 1142–1147, 1981.
31.
HellmerJ, ArnerP, LundinA.Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem177: 132–137, 1989.
32.
LonnrothP, JanssonPA, SmithU.A microdialysis method allowing characterization of intercellular water space in humans. Am J Physiol253: E228–E231, 1987.
33.
NiijimaA.The effect of 2-deoxy-d-glucose and d-glucose on the efferent discharge rate of sympathetic nerves. J Physiol251: 231–243, 1975.
34.
YoshimatsuH, EgawaM, BrayGA. Sympathetic nerve activity after discrete hypothalamic injections of l-glutamate. Brain Res601: 121–128, 1993.
35.
ArrangJM, GarbargM, LancelotJC, LecomteJM, PollardH, RobbaM, SchunackW, SchwartzJC. Highly potent and selective ligands for histamine H3-receptors. Nature327: 117–123, 1987.
InagakiN, YamatodaniA, YamamotoMA, TohyamaM, WatanabeT, WadaH.Organization of histaminergic fibers in the rat brain. J Comp Neurol273: 283–300, 1988.
38.
SakataT, YoshimatsuH, KurokawaM.Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism. Nutrition13: 403–411, 1997.
