Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats.

Abstract:

:Leptin signaling in the hypothalamic arcuate nucleus (ARC) is hypothesized to play an important role in energy homeostasis. To investigate whether leptin signaling limited to this brain area is sufficient to reduce food intake and body weight, we used adenoviral gene therapy to express the signaling isoform of the leptin receptor, lepr(b), in the ARC of leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats. Successful expression of adenovirus containing lepr(b) (Ad-lepr(b)) selectively in the ARC was documented by in situ hybridization. Using real-time PCR, we further demonstrated that bilateral microinjection of Ad-lepr(b) into the ARC restored low hypothalamic levels of lepr(b) mRNA to values approximating those of wild-type (Fa(k)/Fa(k)) controls. Restored leptin receptor expression in the ARC reduced both mean daily food intake (by 13%) and body weight gain (by 33%) and increased hypothalamic proopiomelanocortin mRNA by 65% while decreasing neuropeptide Y mRNA levels by 30%, relative to fa(k)/fa(k) rats injected with a control adenovirus (Ad-lacZ) (P < 0.05 for each comparison). In contrast, Ad-lepr(b) delivery to either the lateral hypothalamic area of fa(k)/fa(k) rats or to the ARC of wild-type Fa(k)/Fa(k) rats had no effect on any of these parameters. These findings collectively support the hypothesis that leptin receptor signaling in the ARC is sufficient to mediate major effects of leptin on long-term energy homeostasis. Adenoviral gene therapy is thus a viable strategy with which to study the physiological importance of specific molecules acting in discrete brain areas.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Morton GJ,Niswender KD,Rhodes CJ,Myers MG Jr,Blevins JE,Baskin DG,Schwartz MW

doi

10.1210/en.2002-0115

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

2016-24

issue

5

eissn

0013-7227

issn

1945-7170

journal_volume

144

pub_type

杂志文章
  • The corpus luteum of the primate menstrual cycle is capable of recovering from a transient withdrawal of pituitary gonadotropin support.

    abstract::To further our understanding of the role of pituitary gonadotropin secretion in the control of corpus luteum function during the primate menstrual cycle, we have used an experimental model which enables us to directly control pituitary gonadotropin secretion throughout the luteal phase. Specifically, we have asked whe...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-117-3-1043

    authors: Hutchison JS,Zeleznik AJ

    更新日期:1985-09-01 00:00:00

  • Almost exclusive androgenic action of dehydroepiandrosterone in the rat mammary gland.

    abstract::To determine the relative role of the androgenic and/or estrogenic components of the action of dehydroepiandrosterone (DHEA) on the histomorphology and structure of the rat mammary gland, ovariectomized (OVX) female animals received DHEA administered alone or in combination with the pure antiandrogen flutamide or the ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.2.5762

    authors: Sourla A,Martel C,Labrie C,Labrie F

    更新日期:1998-02-01 00:00:00

  • Corticosteroidogenesis and adenosine 3', 5'- monophosphate production by the amino-terminal (1-34) fragment of human parathyroid hormone in rat adrenocortical cells.

    abstract::Several studies have revealed a variety of interactions between PTH and ACTH. The existence of a significant area of homology in the bioactive regions of the two molecules has been proposed as a possible reason for such interactions. To clarify the relationship, corticosteroidogenic and cAMP accumulative effects of bo...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-113-3-1036

    authors: Rafferty B,Zanelli JM,Rosenblatt M,Schulster D

    更新日期:1983-09-01 00:00:00

  • Effects of progesterone and tamoxifen on glucocorticosteroid-induced egg-white protein synthesis in the chick oviduct.

    abstract::A single injection of either natural (cortisol, corticosterone) or synthetic [dexamethasone (DEX), triamcinolone acetonide] glucocorticosteroids to estradiol-primed, withdrawn chicks, resulted in a dose-dependent increase in the relative rates of ovalbumin and conalbumin synthesis. The simultaneous injection of equal ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-116-6-2384

    authors: Le Bouc Y,Groyer A,Cadepond F,Groyer-Schweizer G,Robel P,Baulieu EE

    更新日期:1985-06-01 00:00:00

  • Isolation and partial characterization of a porcine parotid hormone that stimulates dentinal fluid transport.

    abstract::A parotid hormone (PH-A beta) has been isolated and purified from porcine parotid glands. The biological effect of the hormone is the stimulation of a dentinal fluid transport (DFT) in molar teeth of rats. The method for purifying the PH-A beta includes: extraction at pH 7 and 5, ultrafiltration through Amicon membran...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-106-6-1994

    authors: Tieche JM,Leonora J,Steinman RR

    更新日期:1980-06-01 00:00:00

  • The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. II. The role of testosterone.

    abstract::The present study was undertaken to evaluate the efficacy of an estradiol-chemical delivery system (E2-CDS) for the brain vs. estradiol benzoate (E2-BNZ) in suppressing serum testosterone (T) and weights of the ventral prostate and seminal vesicle in male rats. Also, the role of serum T in the weight reduction of andr...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-129-2-726

    authors: Anderson WR,Rahimy MH,Brewster ME,Bodor N,Simpkins JW

    更新日期:1991-08-01 00:00:00

  • Impaired leptin expression and abnormal response to fasting in corticotropin-releasing hormone-deficient mice.

    abstract::Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the nee...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-1558

    authors: Jeong KH,Sakihara S,Widmaier EP,Majzoub JA

    更新日期:2004-07-01 00:00:00

  • Some physicochemical characteristics of photoaffinity-labeled rabbit androgen-binding protein.

    abstract::Photoaffinity-labeled androgen-binding protein (ABP), present in cytosol prepared from the caput epididymidis of intact sexually mature rabbits, was produced using 17 beta-hydroxy-[1,2-3H]4,6-androstadien-3-one (delta 6-testosterone). Photo-labeled ABP could not be distinguished from unlabeled ABP by gel filtration ch...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-111-4-1270

    authors: Danzo BJ,Taylor CA Jr,Eller BC

    更新日期:1982-10-01 00:00:00

  • Gonadotropin gene expression and secretion in gonadotropin-releasing hormone antagonist-treated male rats: effect of sex steroid replacement.

    abstract::The possibility of direct pituitary effects of sex steroids on gonadotropin gene expression and synthesis was studied in male rats. The animals were treated with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Org 30276; 0.5 mg/kg BW, sc, twice daily) for 10 days. G...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-6-3204

    authors: Perheentupa A,Huhtaniemi I

    更新日期:1990-06-01 00:00:00

  • The growth hormone (GH) gene is expressed in the lateral hypothalamus: enhancement by GH-releasing hormone and repression by restraint stress.

    abstract::Recent studies suggest that GH may modulate emotion, behavior, or stress response by its direct actions on the brain, and possible expression of the GH gene in the brain has been predicted. In this study we have investigated whether and where the GH gene is expressed in the brain and how it is regulated. Ribonuclease ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.5.6009

    authors: Yoshizato H,Fujikawa T,Soya H,Tanaka M,Nakashima K

    更新日期:1998-05-01 00:00:00

  • Suppression of iodide uptake and thyroid hormone synthesis with stimulation of the type I interferon system by double-stranded ribonucleic acid in cultured human thyroid follicles.

    abstract::Although viral infection is thought to be associated with subacute thyroiditis and probably with autoimmune thyroid disease, possible changes in thyroid function during the prodromal period of infection or subclinical infection remain largely unknown. Recently, it was shown that pathogen-associated molecular patterns ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-1638

    authors: Yamazaki K,Suzuki K,Yamada E,Yamada T,Takeshita F,Matsumoto M,Mitsuhashi T,Obara T,Takano K,Sato K

    更新日期:2007-07-01 00:00:00

  • Angiotensin II and atrial natriuretic factor-binding sites in various tissues in hypertension: comparative receptor localization and changes in different hypertension models in the rat.

    abstract::The peptides angiotensin II (ANGII) and atrial natriuretic factor (ANF) regulate blood pressure and salt and water balance by producing antagonistic physiological effects in a variety of tissues. We used in vitro autoradiography with [125I] ANGII and [125I]ANF to compare receptor regulation for both peptides in variou...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-6-2799

    authors: Wilson SK,Lynch DR,Ladenson PW

    更新日期:1989-06-01 00:00:00

  • The pharmacokinetics of thyrotropin-releasing hormone (TRH) and deamido-TRH in the rat.

    abstract::The pharmacokinetics of TRH and its metabolite deamido-TRH (TRH-OH) were evaluated and compared. After a 60- to 90-min infusion of the appropriate peptide into rats, the MCR, half-life of disappearance (t 1/2), and volume of distribution were calculated. The MCR of TRH averaged 4 ml/min, whereas that of TRH-OH was 6.5...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-115-3-1031

    authors: Safran M,Wu CF,Matys R,Alex S,Emerson CH

    更新日期:1984-09-01 00:00:00

  • Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R- and S-enantiomers on behavior and hormonal response to stress.

    abstract::Estrogens have been shown to have positive and negative effects on anxiety and depressive-like behaviors, perhaps explained by the existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. The ERbeta agonist, diarylpropionitrile (DPN) has been shown to have anxiolytic properties in rats. DPN exists...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-1355

    authors: Weiser MJ,Wu TJ,Handa RJ

    更新日期:2009-04-01 00:00:00

  • The direct in vitro effect of insulin-like growth factors (IGFs) on normal bovine mammary cell proliferation and production of IGF binding proteins.

    abstract::Mammary epithelial cells isolated from pregnant, nonlactating heifers were grown in vitro using collagen substrates. Using these systems, the truncated form of insulin growth factor-1 (IGF-1) (des-3-IGF-1), IGF-1, and IGF-2 all stimulated a significant (0.5 to 1 fold) increase in cell proliferation (des-3-IGF-1 greate...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-129-2-671

    authors: McGrath MF,Collier RJ,Clemmons DR,Busby WH,Sweeny CA,Krivi GG

    更新日期:1991-08-01 00:00:00

  • Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo.

    abstract::Many human breast tumors are driven by high intratumor concentrations of 17beta-estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.4.8091

    authors: James MR,Skaar TC,Lee RY,MacPherson A,Zwiebel JA,Ahluwalia BS,Ampy F,Clarke R

    更新日期:2001-04-01 00:00:00

  • Growth hormone (GH) secretion in the pituitary-grafted male rat: in vivo effects of GH-releasing hormone and isoproterenol and in vitro release by individual somatotropes.

    abstract::Although the pituitary-grafted rat is a classic model of chronic PRL excess, the presence of somatotropes in grafted pituitary tissue indicates a potential for GH secretion. The current study was designed to investigate GH-releasing hormone (GRH)-induced GH secretion and beta-adrenergic inhibition of GH release in ani...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-125-5-2273

    authors: Krieg RJ Jr,Johnson JH,Adler RA

    更新日期:1989-11-01 00:00:00

  • Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts.

    abstract::Women with type 1 diabetes are subfertile. Diabetes negatively affects pregnancy by causing early miscarriage and poor prenatal outcomes. In this study we examine consequences of maternal type 1 diabetes on early embryo development, metabolic gene expression, and the pattern of insulin receptor (IR) and IGF-I receptor...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-0187

    authors: Ramin N,Thieme R,Fischer S,Schindler M,Schmidt T,Fischer B,Navarrete Santos A

    更新日期:2010-09-01 00:00:00

  • Effect of human chorionic gonadotropin and prolactin on 20 alpha-hydroxysteroid dehydrogenase activity in granulosa cells of immature rat ovary.

    abstract::The effects of FSH, hCG, and PRL on the activity of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) of separate ovarian components of hypophysectomized, diethylstilbestrol-treated rats were studied. Enzyme activity was found to reside mainly in granulosa cells. FSH induced an increase in enzyme activity. A prepar...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-104-3-711

    authors: Eckstein B,Nimrod A

    更新日期:1979-03-01 00:00:00

  • Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing.

    abstract::Lefty/Ebaf polypeptides, novel members of the TGF-beta superfamily, are involved in endometrial differentiation and embryo implantation. Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form. Here, we show that decidual differentiation of endom...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0684

    authors: Tang M,Mikhailik A,Pauli I,Giudice LC,Fazelabas AT,Tulac S,Carson DD,Kaufman DG,Barbier C,Creemers JW,Tabibzadeh S

    更新日期:2005-12-01 00:00:00

  • The distinct roles of alpha- and beta-subunits of human thyrotropin in the receptor-binding and postreceptor events.

    abstract::The roles of alpha- and beta-subunits of human TSH (hTSH) were studied by investigating the inhibitory effects of monoclonal antibodies on the biological activity of hTSH. Four monoclonal antibodies directed toward different epitopes on the beta-subunit (hTSH beta) inhibited completely the receptor binding of hTSH to ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-127-1-149

    authors: Endo Y,Tetsumoto T,Nagasaki H,Kashiwai T,Tamaki H,Amino N,Miyai K

    更新日期:1990-07-01 00:00:00

  • Leptin modulates the glucocorticoid-induced ovarian steroidogenesis.

    abstract::Leptin regulates food intake and other activities through its hypothalamic receptor. Leptin receptors are also found in other organs, including the ovary. Direct effects of leptin in ovarian steroid production were studied in primary rat granulosa cells and in rat and human granulosa cell lines. Leptin (0.6-18 nM) sup...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.140.4.6614

    authors: Barkan D,Jia H,Dantes A,Vardimon L,Amsterdam A,Rubinstein M

    更新日期:1999-04-01 00:00:00

  • Short-term adult exposure to estradiol feminizes the male pattern of spontaneous and growth hormone-releasing factor-stimulated growth hormone secretion in the rat.

    abstract::Experimental evidence indicates that the neonatal gonadal steroid environment is an important determinant of the sexual dimorphism of GH secretion and body growth. However, the influence of the sex steroids in GH control during adult life and their mechanism/site of action are largely unknown. In the present study we ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.130.1.1345780

    authors: Painson JC,Thorner MO,Krieg RJ,Tannenbaum GS

    更新日期:1992-01-01 00:00:00

  • Further studies on the action of prolactin on fluid and ion absorption by the rat jejunum.

    abstract::The influence of administration of ovine prolactin in vivo on intestinal fluid and ion transport in vitro was investigated using intact and hypophysectomized male rats. Prolactin administration significantly stimulated fluid, sodium,potassium, calcium, magnesium and chloride transport across everted jejunal sacs. The ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-96-5-1158

    authors: Mainoya JR

    更新日期:1975-05-01 00:00:00

  • Parsing the Potential Neuroendocrine Actions of FGF21 in Primates.

    abstract::Fibroblast growth factor (FGF) 21, a unique, largely liver-derived endocrine member of the FGF superfamily, is often thought of as a fasting factor owing to its induction in rodents during starvation. However, FGF21 is not increased by fasting for periods of <7 days in humans; instead, it rises sharply after acute alc...

    journal_title:Endocrinology

    pub_type: 杂志文章,评审

    doi:10.1210/en.2018-00208

    authors: Gillum MP

    更新日期:2018-05-01 00:00:00

  • Activin A regulates porcine follicle-stimulating hormone beta-subunit transcription via cooperative actions of SMADs and FOXL2.

    abstract::Activins stimulate FSH synthesis and secretion by pituitary gonadotrope cells. Activin A induction of porcine and murine FSHβ (Fshb) gene transcription in immortalized gonadotropes is dependent on homolog of Drosophila mothers against decapentaplegic (SMAD) proteins as well as the forkhead transcription factor L2 (FOX...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-0605

    authors: Lamba P,Wang Y,Tran S,Ouspenskaia T,Libasci V,Hébert TE,Miller GJ,Bernard DJ

    更新日期:2010-11-01 00:00:00

  • Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat adrenocorticotropin response to stressors.

    abstract::We investigated the contribution of corticotropin-releasing factor (CRF) receptors types 1 and 2 (CRF(1) and CRF(2)) in mediating the ACTH response to shock, alcohol injection, or endotoxemia in the rat. Peptidic (Astressin B and Astressin(2)-B) and nonpeptidic (NBI 30775) CRF antagonists were injected iv before the s...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-0117

    authors: Rivier CL,Grigoriadis DE,Rivier JE

    更新日期:2003-06-01 00:00:00

  • Rapid androgenic stimulation of alpha 2u-globulin synthesis in the perfused rat liver.

    abstract::Hepatic synthesis of alpha 2u-globulin and its mRNA in the male rat is dependent on androgen, glucocorticoid, T4, insulin, and GH. Some of these hormones may act directly on the liver, while others may influence alpha 2u-globulin synthesis through indirect physiological changes. In the present study the specific role ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-121-5-1814

    authors: Murty CV,Rao KV,Roy AK

    更新日期:1987-11-01 00:00:00

  • Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function.

    abstract::Two corticotropin-releasing factor 2 receptor (CRF2R)-selective peptides have been recently described, urocortin II (also known as stresscopin-related peptide) and urocortin III (stresscopin). We have used urocortin II to evaluate the effects of activation of the CRF2R on skeletal muscle-related physiological processe...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-0271

    authors: Hinkle RT,Donnelly E,Cody DB,Bauer MB,Isfort RJ

    更新日期:2003-11-01 00:00:00

  • Heterogeneity in mammotrophs prepared from diethylstilbestrol-induced prolactinomas.

    abstract::Pituitary glands from ovariectomized F-344 rats bearing diethylstilbestrol-containing capsules for 70-100 days were dissociated and separated into three size classes by unit gravity sedimentation. The average percentage of large mammotrophs in fraction I was 86 +/- (SE) 2%, the percentage of intermediate-sized mammotr...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-122-5-2324

    authors: Hymer WC,Motter KA

    更新日期:1988-05-01 00:00:00