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  1. Article ; Online: A talk between fat tissue, gut, pancreas and brain to control body weight.

    Wilson, Jenny L / Enriori, Pablo J

    Molecular and cellular endocrinology

    2015  Volume 418 Pt 2, Page(s) 108–119

    Abstract: The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity ... ...

    Abstract The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity and diabetes. A neural network located in the nucleus of the solitary tract-area postrema complex in the hindbrain and the hypothalamus in the forebrain has long been implicated in the control of energy balance. In the hypothalamus this central neuronal network consists of small populations of nuclei with distinct functions such as the arcuate nucleus (ARH), the paraventricular nuclei of the hypothalamus (PVH), the dorsomedial (DMH), the ventromedial (VMH) and the lateral hypothalamus (LH). These hypothalamic areas form interconnected neuronal circuits that respond to fluctuations in energy status by altering the expression of neuropeptides, leading to changes in energy intake and expenditure. Regulation of these hypothalamic nuclei involves the actions of orexigenic peptides (ie ghrelin), which act to stimulate energy intake and decrease energy expenditure, and anorexigenic peptides (ie. leptin and insulin), which act to reduce energy intake and stimulate energy expenditure. Here we review the role of the ARH, DMH and PVH in the control of energy homeostasis and how recent advances in research technologies (Cre-loxP technology, optogenetics and pharmacogenetics) have shed light on the role of these hypothalamic nuclei in the control of energy balance. Such novel findings include the implication of ARH POMC and AgRP neurons in the browning of white adipose tissue to regulate energy expenditure as well as the likely existence of divergent hypothalamic pathways in the DMH and PVH in the control of food intake and energy expenditure.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Arcuate Nucleus of Hypothalamus/metabolism ; Body Weight/physiology ; Brain/metabolism ; Dorsomedial Hypothalamic Nucleus/metabolism ; Energy Intake ; Energy Metabolism ; Humans ; Hypothalamus/metabolism ; Leptin/metabolism ; Pancreas/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism
    Chemical Substances Leptin
    Language English
    Publishing date 2015-12-15
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2015.08.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance.

    Loh, Kim / Fukushima, Atsushi / Zhang, Xinmei / Galic, Sandra / Briggs, Dana / Enriori, Pablo J / Simonds, Stephanie / Wiede, Florian / Reichenbach, Alexander / Hauser, Christine / Sims, Natalie A / Bence, Kendra K / Zhang, Sheng / Zhang, Zhong-Yin / Kahn, Barbara B / Neel, Benjamin G / Andrews, Zane B / Cowley, Michael A / Tiganis, Tony

    Cell metabolism

    2022  Volume 34, Issue 11, Page(s) 1892

    Language English
    Publishing date 2022-11-02
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2022.09.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Leptin increasing sympathetic nerve outflow in obesity: A cure for obesity or a potential contributor to metabolic syndrome?

    Simonds, Stephanie E / Cowley, Michael A / Enriori, Pablo J

    Adipocyte

    2013  Volume 1, Issue 3, Page(s) 177–181

    Abstract: Obesity is a global problem and effective drug therapy treatment is still unavailable. Obesity develops due to an imbalance between energy intake and energy expenditure (EE). Understanding what happens to EE in obesity may be the key to developing new ... ...

    Abstract Obesity is a global problem and effective drug therapy treatment is still unavailable. Obesity develops due to an imbalance between energy intake and energy expenditure (EE). Understanding what happens to EE in obesity may be the key to developing new treatments for obesity. If EE in obesity can be elevated, it could be a potential therapeutic target. We recently discovered that in baseline conditions obese mice have increased EE, in terms of thermogenesis. However, this increase in EE is not great enough to offset the elevated calorie intake that leads to the development of obesity. In obesity, the adipose derived hormone leptin is significantly elevated. This elevated leptin concentration appears to cause an increase in thermogenesis through increased sympathetic nerve activity (SNA) to brown adipose tissue deposits. The brain region of the dorsomedial hypothalamus (DMH) appears to be a key region that leptin activates in obesity to cause this increased thermogenesis. One unsettling finding is that the sympathetic nervous system (SNS) in obesity is elevated via leptin and it seems unlikely that SNA would be selectivity increased to only brown adipose tissue. Previously, it has been observed that leptin can increase SNA to numerous organs including the kidney. Furthermore, in obesity, SNA is increased in numerous organs. This leads to the critical question: is the leptin-mediated elevation of SNA and thermogenesis also chronically activating the kidney and contributing to the development of hypertension in obesity?
    Language English
    Publishing date 2013-05-24
    Publishing country United States
    Document type Journal Article
    ISSN 2162-3945
    ISSN 2162-3945
    DOI 10.4161/adip.20690
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The pathogenesis of osteoporosis in older women and men: a review.

    Enriori, Pablo J / Enriori, Carlos L

    The Journal of steroid biochemistry and molecular biology

    2002  Volume 82, Issue 1, Page(s) 1–6

    MeSH term(s) Aged ; Female ; Humans ; Male ; Osteoporosis/etiology ; Osteoporosis, Postmenopausal/etiology
    Language English
    Publishing date 2002-10-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/s0960-0760(02)00144-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: A talk between fat tissue, gut, pancreas and brain to control body weight

    Wilson, Jenny L / Pablo J. Enriori

    Molecular and Cellular Endocrinology. 2015 Dec. 15, v. 418

    2015  

    Abstract: The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity ... ...

    Abstract The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity and diabetes. A neural network located in the nucleus of the solitary tract–area postrema complex in the hindbrain and the hypothalamus in the forebrain has long been implicated in the control of energy balance. In the hypothalamus this central neuronal network consists of small populations of nuclei with distinct functions such as the arcuate nucleus (ARH), the paraventricular nuclei of the hypothalamus (PVH), the dorsomedial (DMH), the ventromedial (VMH) and the lateral hypothalamus (LH). These hypothalamic areas form interconnected neuronal circuits that respond to fluctuations in energy status by altering the expression of neuropeptides, leading to changes in energy intake and expenditure. Regulation of these hypothalamic nuclei involves the actions of orexigenic peptides (ie ghrelin), which act to stimulate energy intake and decrease energy expenditure, and anorexigenic peptides (ie. leptin and insulin), which act to reduce energy intake and stimulate energy expenditure. Here we review the role of the ARH, DMH and PVH in the control of energy homeostasis and how recent advances in research technologies (Cre-loxP technology, optogenetics and pharmacogenetics) have shed light on the role of these hypothalamic nuclei in the control of energy balance. Such novel findings include the implication of ARH POMC and AgRP neurons in the browning of white adipose tissue to regulate energy expenditure as well as the likely existence of divergent hypothalamic pathways in the DMH and PVH in the control of food intake and energy expenditure.
    Keywords diabetes ; energy expenditure ; energy intake ; food intake ; ghrelin ; homeostasis ; hypothalamic regulation ; hypothalamus ; insulin ; leptin ; neural networks ; neurons ; neuropeptides ; obesity ; optogenetics ; pancreas ; pandemic ; pharmacogenomics ; white adipose tissue
    Language English
    Dates of publication 2015-1215
    Size p. 108-119.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2015.08.022
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Neural Plasticity in Obesity and Psychiatric Disorders.

    Arcos-Burgos, Mauricio / Acosta, Maria T / Martinez, Ariel F / Muenke, Maximilian / Enriori, Pablo J / Mastronardi, Claudio A

    Neural plasticity

    2016  Volume 2016, Page(s) 6053871

    MeSH term(s) Brain/physiopathology ; Humans ; Mental Disorders/physiopathology ; Neuronal Plasticity/physiology ; Obesity/physiopathology
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Editorial
    ZDB-ID 1454938-4
    ISSN 1687-5443 ; 2090-5904 ; 0792-8483
    ISSN (online) 1687-5443
    ISSN 2090-5904 ; 0792-8483
    DOI 10.1155/2016/6053871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Aldosterone-Mediated Renal Sodium Transport Requires Intact Mineralocorticoid Receptor DNA-Binding in the Mouse.

    Cole, Timothy J / Terella, Luke / Morgan, James / Alexiadis, Maria / Yao, Yi-Zhou / Enriori, Pablo / Young, Morag J / Fuller, Peter J

    Endocrinology

    2015  Volume 156, Issue 8, Page(s) 2958–2968

    Abstract: The classic role of mineralocorticoid receptor (MR) is to promote sodium transport in epithelial tissues. However, the MR is also expressed in a range of tissues in which its role appears unrelated to sodium transport, and under normal physiological ... ...

    Abstract The classic role of mineralocorticoid receptor (MR) is to promote sodium transport in epithelial tissues. However, the MR is also expressed in a range of tissues in which its role appears unrelated to sodium transport, and under normal physiological conditions, it may be responding to cortisol (corticosterone in rodents) rather than aldosterone. The relative importance of transcriptional mechanisms such as classical genomic signaling via a hormone response element, transrepression of other transcription factors, and nongenomic signaling is not clear, particularly in nonepithelial tissues. The goal of the present study was to define the role of the different signaling pathways for the MR by separating the functional role of classic genomic signaling, mediated by DNA binding, from these two other mechanisms. We used gene targeting to generate mice in which serine is substituted for cysteine at codon 603 in the MR; this mutation precludes DNA binding. These MR C603S mutant mice either die at birth or fail to thrive, lose weight, and die between days 10 and 13 in a manner similar to that observed previously for mice null for the MR gene. Renal expression and cellular localization of MR C603S by immunohistochemistry was equivalent to control mice. MR C603S mice were rescued by twice-daily saline injections. Despite increased aldosterone levels, renal expression of aldosterone-induced genes was not increased. This unique mouse model demonstrates that DNA binding is essential for the epithelial MR response and will provide the basis for analysis of nonclassical signaling of the MR in nonepithelial tissues.
    MeSH term(s) Aldosterone/pharmacology ; Amino Acid Sequence ; Animals ; DNA/metabolism ; Gene Expression Regulation/drug effects ; Gene Knock-In Techniques ; Ion Transport/drug effects ; Ion Transport/genetics ; Kidney/drug effects ; Kidney/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation, Missense ; Protein Binding/drug effects ; Protein Interaction Domains and Motifs/genetics ; Receptors, Mineralocorticoid/genetics ; Receptors, Mineralocorticoid/metabolism ; Sodium/metabolism ; Zinc Fingers/genetics
    Chemical Substances Receptors, Mineralocorticoid ; Aldosterone (4964P6T9RB) ; DNA (9007-49-2) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2015-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2015-1008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Changes of dipeptidyl peptidase IV (DPP-IV) in obese children with weight loss: relationships to peptide YY, pancreatic peptide, and insulin sensitivity.

    Reinehr, Thomas / Roth, Christian L / Enriori, Pablo J / Masur, Kai

    Journal of pediatric endocrinology & metabolism : JPEM

    2010  Volume 23, Issue 1-2, Page(s) 101–108

    Abstract: Aim: Gastrointestinal (GI) hormones are involved in satiety regulation and in glucose metabolism. Most GI hormones are hydrolyzed and inactivated by the same enzyme, dipeptidyl peptidase IV (DPP-IV). We analyzed changes of DPP-IV after weight loss in ... ...

    Abstract Aim: Gastrointestinal (GI) hormones are involved in satiety regulation and in glucose metabolism. Most GI hormones are hydrolyzed and inactivated by the same enzyme, dipeptidyl peptidase IV (DPP-IV). We analyzed changes of DPP-IV after weight loss in obese children and its relationships to the GI hormones pancreatic peptide (PP), peptide YY (PYY), and insulin sensitivity.
    Methods: We measured at baseline and one year later anthropometrics, percentage body fat based on skinfold thickness, DPP-IV, PP, PYY, insulin, and glucose concentrations in 18 obese children (mean age 10.9 years, 44% male, mean BMI 28.5 kg/m2) who participated in a one-year lifestyle intervention program based on physical activity, nutrition course, and behavioral therapy. Insulin sensitivity was calculated using QUICKI.
    Results: Changes of DPP-IV correlated significantly to the changes of percentage body fat (r = 0.47) and BMI SDS (r = 0.60). In partial regression analysis adjusted for change in weight status, changes of DPP-IV correlated significantly to changes of PYY (r = -0.43), PP (r = -0.49), QUICKI (r = -0.53), and insulin (r = 0.57). The 10 children with substantial weight loss significantly reduced their DPP-IV and insulin concentrations, while QUICKI, PYY, and PP levels significantly increased. In children without substantial weight loss no significant changes were observed.
    Conclusions: These findings suggest that the increase of fasting PP and PYY in weight loss is influenced at least in part by a decrease of their cleavage enzyme DPP-IV. Further research is necessary to evaluate the mechanisms in weight loss leading to a decrease of DPP-IV activity and consequently to an improvement of insulin sensitivity.
    MeSH term(s) Adolescent ; Ambulatory Care ; Blood Glucose/metabolism ; Child ; Child Health Services ; Dipeptidyl Peptidase 4/blood ; Female ; Humans ; Insulin/blood ; Insulin Resistance ; Life Style ; Male ; Obesity/blood ; Obesity/therapy ; Pancreatic Polypeptide/blood ; Peptide YY/blood ; Treatment Outcome ; Weight Loss
    Chemical Substances Blood Glucose ; Insulin ; Peptide YY (106388-42-5) ; Pancreatic Polypeptide (59763-91-6) ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
    Language English
    Publishing date 2010-04-23
    Publishing country Germany
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1231070-0
    ISSN 2191-0251 ; 0334-018X
    ISSN (online) 2191-0251
    ISSN 0334-018X
    DOI 10.1515/jpem.2010.23.1-2.101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Abdominal fat analyzed by DEXA scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice.

    Chen, Weiyi / Wilson, Jenny L / Khaksari, Mohammad / Cowley, Michael A / Enriori, Pablo J

    American journal of physiology. Endocrinology and metabolism

    2012  Volume 303, Issue 5, Page(s) E635–43

    Abstract: Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited ... ...

    Abstract Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited methods for the noninvasive measurement of fat distribution in mice. Although micromagnetic resonance imaging and microcomputed tomography are the "gold standards" in the measurement of fat distribution, more economical and accessible methods are required. Dual energy X-ray absorptiometry (DEXA) is an effective method in characterizing fat content; however, it cannot discriminate between visceral and subcutaneous fat depots. We demonstrate that an evaluation of abdominal fat content measured by DEXA through the selection of one localized abdominal area strongly correlates with visceral fat content in C57BL/6J mice. We found that DEXA is able to measure fat pad volume ex vivo with high accuracy; however, the measurement of visceral fat in vivo shows an overestimation caused by subcutaneous tissue interference. The overestimation is almost constant for a wide range of values, and thus it is possible to correct the data for a more accurate estimation of visceral fat content. We demonstrate the utility of this technique in characterizing phenotypes of several obese mouse models (ob/ob, db/db, MC4R-KO, and DIO) and evaluating the effect of treatments on visceral fat content in longitudinal studies. Additionally, we also establish abdominal obesity as a potential biomarker for metabolic abnormalities (liver fat accumulation, insulin resistance/diabetes) in mice, similar to that described in humans.
    MeSH term(s) Absorptiometry, Photon/methods ; Adiposity ; Animals ; Disease Models, Animal ; Female ; Insulin Resistance ; Intra-Abdominal Fat/diagnostic imaging ; Lipid Metabolism ; Liver/metabolism ; Male ; Metabolic Diseases/diagnostic imaging ; Metabolic Diseases/metabolism ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Mice, Obese ; Obesity, Abdominal/diagnostic imaging ; Obesity, Abdominal/metabolism ; Reproducibility of Results ; Sex Characteristics ; Subcutaneous Fat, Abdominal/diagnostic imaging ; Whole Body Imaging
    Language English
    Publishing date 2012-07-03
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Validation Study
    ZDB-ID 603841-4
    ISSN 1522-1555 ; 0193-1849
    ISSN (online) 1522-1555
    ISSN 0193-1849
    DOI 10.1152/ajpendo.00078.2012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Excess of nerve growth factor in the ovary causes a polycystic ovary-like syndrome in mice, which closely resembles both reproductive and metabolic aspects of the human syndrome.

    Wilson, Jenny L / Chen, Weiyi / Dissen, Gregory A / Ojeda, Sergio R / Cowley, Michael A / Garcia-Rudaz, Cecilia / Enriori, Pablo J

    Endocrinology

    2014  Volume 155, Issue 11, Page(s) 4494–4506

    Abstract: Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and ... ...

    Abstract Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and dyslipidemia. We previously reported that transgenic overexpression of nerve growth factor (NGF), a marker of sympathetic hyperactivity, directed to the ovary by the mouse 17α-hydroxylase/C17-20 lyase promoter (17NF mice), results in ovarian abnormalities similar to those seen in PCOS women. To investigate whether ovarian overproduction of NGF also induces common metabolic alterations of PCOS, we assessed glucose homeostasis by glucose tolerance test, plasma insulin levels, and body composition by dual-energy x-ray absorptiometry scan in young female 17NF mice and wild-type mice. 17NF mice exhibited increased body weight and alterations in body fat distribution with a greater accumulation of visceral fat compared with sc fat (P < .01). 17NF mice also displayed glucose intolerance (P < .01), decreased insulin-mediated glucose disposal (P < .01), and hyperinsulinemia (P < .05), which, similar to PCOS patients, occurred independently of body weight. Additionally, 17NF mice exhibited increased sympathetic outflow observed as increased interscapular brown adipose tissue temperature. This change was evident during the dark period (7 pm to 7 am) and occurred concomitant with increased interscapular brown adipose tissue uncoupling protein 1 expression. These findings suggest that overexpression of NGF in the ovary may suffice to cause both reproductive and metabolic alterations characteristic of PCOS and support the hypothesis that sympathetic hyperactivity may contribute to the development and/or progression of PCOS.
    MeSH term(s) Animals ; Disease Models, Animal ; Female ; Humans ; Infertility, Female/genetics ; Infertility, Female/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Growth Factor/genetics ; Nerve Growth Factor/metabolism ; Ovary/metabolism ; Ovary/pathology ; Phenotype ; Polycystic Ovary Syndrome/genetics ; Polycystic Ovary Syndrome/metabolism ; Polycystic Ovary Syndrome/pathology ; Reproduction/genetics ; Up-Regulation/genetics
    Chemical Substances Nerve Growth Factor (9061-61-4)
    Language English
    Publishing date 2014-09-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2014-1368
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