DOCSLIB.ORG

Leptin Replacement Reestablishes Brain Insulin Action in The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Leptin Replacement Reestablishes Brain Insulin Action in The Diabetes Care 1 Sabine Frank-Podlech,1–3 Leptin Replacement Reestablishes Julia von Schnurbein,4 Ralf Veit,1–3 Martin Heni,2,3 Jurgen¨ Machann,2,5 Brain Insulin Action in the Jaana M. Heinze,2,3 Stephanie Kullmann,2,3 Jaida Manzoor,6 Hypothalamus in Congenital Saqib Mahmood,7 Hans-Ulrich Haring,¨ 2,3 fi Hubert Preissl,2,3,8,9 Martin Wabitsch,4 Leptin De ciency and Andreas Fritsche2,3 https://doi.org/10.2337/dc17-1867 OBJECTIVE Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral 1 metabolism. Institute for Medical Psychology and Behaviou- ral Neurobiology, University of Tubingen,¨ Tubingen,¨ Germany RESEARCH DESIGN AND METHODS 2 Institute for Diabetes Research and Metabolic In a leptin-deficient patient, we investigated the impact of leptin substitution on Diseases of the Helmholtz Center Munich at the central insulin action, as quantified by changes in neuronal activity after intranasal University of Tubingen,¨ German Center for Dia- insulin application. This was assessed before and during the 1st year of metreleptin betes Research, Tubingen,¨ Germany 3Department of Internal Medicine IV, University substitution. Hospital, Tubingen,¨ Germany 4Division of Pediatric Endocrinology and Diabe- RESULTS tes, Department of Pediatrics and Adolescent After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, Medicine, University of Ulm, Ulm, Germany 5 particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Section on Experimental Radiology, Depart- ment of Diagnostic and Interventional Radiol- Results are depicted in comparison with a control group. In our patient, brain acti- ogy, University Hospital, Tubingen,¨ Germany NOVEL COMMUNICATIONS IN DIABETES vation changes were accompanied by substantial weight loss, reduced visceral adi- 6Children Hospital the Institute of Child Health, pose tissue, reduced intrahepatic lipid content, and improved whole-body insulin Lahore, Pakistan 7Department of Human Genetics and Molecular sensitivity. Biology, University of Health Sciences, Khayaban- e-Jamia Punjab, Lahore, Pakistan CONCLUSIONS 8Institute for Diabetes and Obesity, Helmholtz Leptin replacement and weight loss improved homeostatic insulin action in the Diabetes Center, Helmholtz Center Munich, Ger- patient in question. man Research Center for Environmental Health, Neuherberg, Germany 9Department Pharmacy and Biochemistry, Fac- ulty of Science, University of Tubingen,¨ Tubingen,¨ Patients affected by monogenetic leptin deficiency, whose leptin levels are therefore Germany practically indiscernible, suffer from severe obesity, hyperphagia, impaired satiety, and Corresponding Author: Sabine Frank-Podlech, metabolic impairments such as peripheral insulin resistance (1). Leptin replacement [email protected]. therapy is known to improve metabolism, normalize body weight, and introduce Received 7 September 2017 and accepted 26 changes in brain processes (2–5). In recent years, we and others have ascertained December 2017. that brain insulin action is crucial to various aspects of behavior and metabolism, S.F.-P. and J.v.S. contributed equally to this such as eating behavior, cognition, and whole-body metabolism (6,7). However, brain study. M.W. and A.F. contributed equally to this insulin action, which is quantified by changes in neuronal activity in the functional MRI, study. had never been assessed both before and after leptin replacement therapy in congen- © 2018 by the American Diabetes Association. ital leptin-deficient patients. On the basis of the close molecular interaction of brain Readers may use this article as long as the work fi is properly cited, the use is educational and not leptin and insulin signaling (8), we hypothesized that the untreated leptin-de cient for profit, and the work is not altered. More infor- patient will be brain insulin resistant, which can be reverted by substitution of leptin mation is available at http://www.diabetesjournals with metreleptin, a synthetic leptin analog. .org/content/license. Diabetes Care Publish Ahead of Print, published online January 24, 2018 2 Brain Insulin Sensitivity in Leptin Deficiency Diabetes Care RESEARCH DESIGN AND METHODS z = 31) as a center with a sphere of CONCLUSIONS We performed resting functional MRI 6 mm for the PFC mask (9). Perfusion val- Congenital leptin deficiency is character- measurements on a leptin-deficient 31- ues were extracted for each voxel within ized by various metabolic impairments, in year-old Pakistani woman before therapy the masks for all measurements. Further- particular those associated with energy ho- (leptin-deficient untreated state), as well more, whole-brain mean perfusion was meostasis and peripheral insulin action. as 7 days after and 1 year after onset of calculated to standardize each extracted Earlier studies have shown not only weight substitution with 1.8 mg metreleptin. perfusion value for global perfusion dif- loss but also a marked improvement in Brain insulin sensitivity was assessed by ferences between measurements (rela- whole-body metabolic functions, e.g., insu- the quantification of cerebral blood flow tive perfusion values). Data were further lin sensitivity, reduction of visceral and liver (CBF) pre– and 30 min post–intranasal in- analyzed in SPSS 24 (IBM Corporation, fat, and behavioral changes once metre- sulin application (160 units) by a nasal Armonk, NY) using a sign test to investi- leptin substitution wasinitiated(12,13). spray (details in 9). Blood samples were gate the change in relative perfusion in In the current study, we show that brain taken before the first measurement to each voxel within each region of interest insulin action was impaired in a leptin- , determine peripheral glucose and insulin (P 0.05, Bonferroni corrected). deficient patient before, as well as 7 days fi levels. Fasting HOMA of insulin resistance For the quanti cation of visceral adi- after, metreleptin substitution. Interest- (HOMA-IR) was calculated for each mea- pose tissue (VAT) and intrahepatic lipids ingly, 1 year after metreleptin treatment, surement day [fasting insulin (pmol/L/ (IHL), abdominal MRI and localized pro- brain insulin action showed a marked re- ton MRS measurements were performed 6.945) * fasting glucose (mg/dL)/405] to duction in hypothalamic CBF but higher (12). estimate peripheral insulin sensitivity. PFC activity after insulin application. For interpretation of the results of the Scanning was performed on a 3T whole- Before and especially after 7 days patient from the perspective of “healthy” body scanner with a standard 20-channel of metreleptin substitution, our patient women, unpublished data of a female con- head coil (MAGNETOM Prisma, Siemens, showed an increase in hypothalamic CBF trol group from a previous study (9) are Erlangen, Germany). CBF was measured that exceeded even the highest increase included for results presentation (N =21; with a three-dimensional fast spin-echo se- of subjects of a healthy control group. By mean 6 SD BMI 26.5 6 5.5 kg/m2 and age quence using the FAIR QII perfusion mode contrast, after 1 year of treatment, our 26.1 6 3.6 years) (methods described with three-dimensional readout (3D patient showed the anticipated decrease in 9). GRASE). In addition, a high-resolution T1- in perfusion after intranasal insulin appli- weighted anatomical image was acquired. cation. This result corresponds to the con- CBF image processing was performed RESULTS trol subjects with the highest brain insulin using FSL (http://fsl.fmrib.ox.ac.uk) and Analyses showed increased relative sensitivity (and thus with reduced hypo- fi SPM12 (http://www. l.ion.ucl.ac.uk./spm). perfusion after intranasal insulin applica- thalamic activity after insulin application) Images from each session were realigned tion in the hypothalamus in the leptin- (Fig. 1C). It is well established that the two and resliced using FLIRT. Perfusion images deficient state and 7 days after initiation anorectic hormones insulin and leptin were calculated by pairwise subtraction of metreleptin treatment. After 1 year, closely interact with each other in the hy- of the motion-corrected control and label intranasal insulin had effected a marked pothalamus and share molecular signaling images with ASL_FILE. The OXFORD_ASL reduction of relative perfusion in the pathways in neurons and nonneuronal moduleinFSLwasusedtocalculateresting- hypothalamus (Fig. 1A). No significant ef- cells (8). Furthermore, animal (8) and first state perfusion maps. Perfusion analysis fect of insulin application was observed human (6,7,14) data indicate a modula- was restricted by including only voxels for the PFC in either the leptin-deficient tion of peripheral insulin sensitivity by that were classified with a probability of state or 7 days after the onset of treat- the brain. Thus, the improvement in pe- at least 75% of being gray matter on the ment. After 1 year, however, insulin had ripheral insulin sensitivity after 1 year of basis of T1-weighted, anatomical images induced an increase in relative PFC perfu- metreleptin treatment observed in our (10). The perfusion maps of each session sion (Fig. 1B). patient might be due to restored brain and day were then individually coregistered As can be observed in Fig. 1C,hypotha- insulin action. However, improved insulin to the anatomical image and normalized to lamic activity increase
Load more

Recommended publications
  • Associations Between Serum Leptin Level and Bone Turnover in Kidney Transplant Recipients
    Associations between Serum Leptin Level and Bone Turnover in Kidney Transplant Recipients ʈ ʈ ʈ Csaba P. Kovesdy,*† Miklos Z. Molnar,‡§ Maria E. Czira, Anna Rudas, Akos Ujszaszi, Laszlo Rosivall,‡ Miklos Szathmari,¶ Adrian Covic,** Andras Keszei,†† Gabriella Beko,‡‡ ʈ Peter Lakatos,¶ Janos Kosa,¶ and Istvan Mucsi §§ *Division of Nephrology, Salem Veterans Affairs Medical Center, Salem, Virginia; †Division of Nephrology, University of Virginia, Charlottesville, Virginia; ‡Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; §Harold Simmons Center for Chronic Disease Research & Epidemiology, Los Angeles Biomedical Research Institute at ʈ Harbor-University of California–Los Angeles Medical Center, Torrance, California; Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary; ¶First Department of Internal Medicine, Semmelweis University, Budapest, Hungary; **University of Medicine Gr T Popa, Iasi, Romania; ††Department of Epidemiology, Maastricht University, Maastricht, Netherlands; ‡‡Central Laboratory, Semmelweis University, Budapest, Hungary; and §§Division of Nephrology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada Background and objectives: Obesity is associated with increased parathyroid hormone (PTH) in the general population and in patients with chronic kidney disease (CKD). A direct effect of adipose tissue on bone turnover through leptin production has been suggested, but such an association has not been explored in kidney transplant recipients. Design, setting, participants, & measurements: This study examined associations of serum leptin with PTH and with biomarkers of bone turnover (serum beta crosslaps [CTX, a marker of bone resorption] and osteocalcin [OC, a marker of bone formation]) in 978 kidney transplant recipients. Associations were examined in multivariable regression models. Path analyses were used to determine if the association of leptin with bone turnover is independent of PTH.
    [Show full text]
  • Low Ambient Temperature Lowers Cholecystokinin and Leptin Plasma Concentrations in Adult Men Monika Pizon, Przemyslaw J
    The Open Nutrition Journal, 2009, 3, 5-7 5 Open Access Low Ambient Temperature Lowers Cholecystokinin and Leptin Plasma Concentrations in Adult Men Monika Pizon, Przemyslaw J. Tomasik*, Krystyna Sztefko and Zdzislaw Szafran Department of Clinical Biochemistry, University Children`s Hospital, Krakow, Poland Abstract: Background: It is known that the low ambient temperature causes a considerable increase of appetite. The mechanisms underlying the changes of the amounts of the ingested food in relation to the environmental temperature has not been elucidated. The aim of this study was to investigate the effect of the short exposure to low ambient temperature on the plasma concentration of leptin and cholecystokinin. Methods: Sixteen healthy men, mean age 24.6 ± 3.5 years, BMI 22.3 ± 2.3 kg/m2, participated in the study. The concen- trations of plasma CCK and leptin were determined twice – before and after the 30 min. exposure to + 4 °C by using RIA kits. Results: The mean value of CCK concentration before the exposure to low ambient temperature was 1.1 pmol/l, and after the exposure 0.6 pmol/l (p<0.0005 in the paired t-test). The mean values of leptin before exposure (4.7 ± 1.54 μg/l) were also significantly lower than after the exposure (6.4 ± 1.7 μg/l; p<0.0005 in the paired t-test). However no significant cor- relation was found between CCK and leptin concentrations, both before and after exposure to low temperature. Conclusions: It has been known that a fall in the concentration of CCK elicits hunger and causes an increase in feeding activity.
    [Show full text]
  • Metabolic Regulation of Fertility Through Presynaptic and Postsynaptic Signaling to Gonadotropin-Releasing Hormone Neurons
    8578 • The Journal of Neuroscience, September 17, 2003 • 23(24):8578–8585 Behavioral/Systems/Cognitive Metabolic Regulation of Fertility through Presynaptic and Postsynaptic Signaling to Gonadotropin-Releasing Hormone Neurons Shannon D. Sullivan, R. Anthony DeFazio, and Suzanne M. Moenter 1Internal Medicine and Cell Biology, University of Virginia, Charlottesville, Virginia 22908 Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction and are inhibited by negative energy balance. In normal adults, these neurons maintain elevated intracellular chloride so that GABAA receptor activation is excitatory. We hypothesized that fasting alters homeostatic mechanisms to eliminate excitatory responses to GABA but rejected this hypothesis when brief, local GABA application elicited action currents in GnRH neurons from fed and fasted mice. This response was specific to GABAA receptors, because glycine elicited no response. We next found that fasting reduced the frequency of spontaneous GABAergic postsynaptic currents (PSCs) and that this was reversed by in vivo treatment with leptin during the fast. In the presence of tetrodotoxin to minimize presynaptic actions, leptin also potentiated the postsynaptic response of these cells to GABAA receptor activation. Postsynaptic effects of leptin on GABAergic miniature PSCs were eliminated by inhibiting JAK2/3 (Janus kinase), the tyrosine kinase through which leptin receptors signal. In all experiments, elimination of PSCs at ECl or by treatment with the GABAA receptor antagonist bicuculline confirmed that PSCs were specifically mediated by GABAA receptor chloride channels. These data dem- onstrate that fasting and leptin act presynaptically and postsynaptically to alter GABAergic drive to GnRH neurons, providing evidence for GABAergic communication of metabolic cues to GnRH neurons, and suggest the possibility for functional leptin receptors on GnRH neurons.
    [Show full text]
  • Insulin and Leptin As Adiposity Signals
    Insulin and Leptin as Adiposity Signals STEPHEN C. BENOIT,DEBORAH J. CLEGG,RANDY J. SEELEY, AND STEPHEN C. WOODS Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 ABSTRACT There is now considerable consensus that the adipocyte hormone leptin and the pancreatic hormone insulin are important regulators of food intake and energy balance. Leptin and insulin fulfill many of the requirements to be putative adiposity signals to the brain. Plasma leptin and insulin levels are positively correlated with body weight and with adipose mass in particular. Furthermore, both leptin and insulin enter the brain from the plasma. The brain expresses both insulin and leptin receptors in areas important in the control of food intake and energy balance. Consistent with their roles as adiposity signals, exogenous leptin and insulin both reduce food intake when administered locally into the brain in a number of species under different experimental paradigms. Additionally, central administration of insulin antibodies increases food intake and body weight. Recent studies have demonstrated that both insulin and leptin have additive effects when administered simulta- neously. Finally, we recently have demonstrated that leptin and insulin share downstream neuropep- tide signaling pathways. Hence, insulin and leptin provide important negative feedback signals to the central nervous system, proportional to peripheral energy stores and coupled with catabolic circuits. I. Overview When maintained on an ad libitum diet, most animals — including humans — are able to precisely match caloric intake with caloric expenditure, resulting in relatively stable energy stores as adipose tissue (Kennedy, 1953; Keesey, 1986). Growing emphasis has been placed on the role of the central nervous system (CNS) in controlling this precision of energy homeostasis.
    [Show full text]
  • Neuropeptide Y and Peptide YY in Association with Depressive
    nutrients Article Neuropeptide Y and Peptide YY in Association with Depressive Symptoms and Eating Behaviours in Adolescents across the Weight Spectrum: From Anorexia Nervosa to Obesity Marta Tyszkiewicz-Nwafor 1,* , Katarzyna Jowik 1, Agata Dutkiewicz 1, Agata Krasinska 2 , Natalia Pytlinska 1, Monika Dmitrzak-Weglarz 3, Marta Suminska 2 , Agata Pruciak 4, Bogda Skowronska 2,† and Agnieszka Slopien 1,† 1 Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, 61-701 Poznan, Poland; [email protected] (K.J.); [email protected] (A.D.); [email protected] (N.P.); [email protected] (A.S.) 2 Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, 61-701 Poznan, Poland; [email protected] (A.K.); [email protected] (M.S.); [email protected] (B.S.) 3 Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, 61-701 Poznan, Poland; [email protected] 4 Institute of Plant Protection—National Research Institute, Research Centre of Quarantine, Invasive and Genetically Modified Organisms, 60-318 Poznan, Poland; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Citation: Tyszkiewicz-Nwafor, M.; Jowik, K.; Dutkiewicz, A.; Krasinska, Abstract: Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The A.; Pytlinska, N.; Dmitrzak-Weglarz, purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia M.; Suminska, M.; Pruciak, A.; nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential Skowronska, B.; Slopien, A. confounders on their concentrations were also analysed.
    [Show full text]
  • Intracellular Interplay Between Cholecystokinin and Leptin Signalling for Satiety Control in Rats
    www.nature.com/scientificreports OPEN Intracellular interplay between cholecystokinin and leptin signalling for satiety control in rats Hayato Koizumi1,2, Shahid Mohammad1,3, Tomoya Ozaki 1,4, Kiyokazu Muto2, Nanami Matsuba2, Juhyon Kim1,2, Weihong Pan5,6, Eri Morioka2, Takatoshi Mochizuki2 & Masayuki Ikeda1,2* Cholecystokinin (CCK) and leptin are satiety-controlling peptides, yet their interactive roles remain unclear. Here, we addressed this issue using in vitro and in vivo models. In rat C6 glioma cells, leptin pre-treatment enhanced Ca2+ mobilization by a CCK agonist (CCK-8s). This leptin action was reduced by Janus kinase inhibitor (AG490) or PI3-kinase inhibitor (LY294002). Meanwhile, leptin stimulation alone failed to mobilize ­Ca2+ even in cells overexpressing leptin receptors (C6-ObRb). Leptin increased nuclear immunoreactivity against phosphorylated STAT3 (pSTAT3) whereas CCK-8s reduced leptin-induced nuclear pSTAT3 accumulation in these cells. In the rat ventromedial hypothalamus (VMH), leptin-induced action potential fring was enhanced, whereas nuclear pSTAT3 was reduced by co-stimulation with CCK-8s. To further analyse in vivo signalling interplay, a CCK-1 antagonist (lorglumide) was intraperitoneally injected in rats following 1-h restricted feeding. Food access was increased 3-h after lorglumide injection. At this timepoint, nuclear pSTAT3 was increased whereas c-Fos was decreased in the VMH. Taken together, these results suggest that leptin and CCK receptors may both contribute to short-term satiety, and leptin could positively modulate CCK signalling. Notably, nuclear pSTAT3 levels in this experimental paradigm were negatively correlated with satiety levels, contrary to the generally described transcriptional regulation for long-term satiety via leptin receptors.
    [Show full text]
  • Appetite Hormones and the Transition to Hyperphagia in Children with Prader-Willi Syndrome
    International Journal of Obesity (2012) 36, 1564 --1570 & 2012 Macmillan Publishers Limited All rights reserved 0307-0565/12 www.nature.com/ijo ORIGINAL ARTICLE Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome AP Goldstone1, AJ Holland2, JV Butler2 and JE Whittington2 OBJECTIVE: Prader--Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS. SUBJECTS: In this cross-sectional study, children with PWS (n ¼ 42) and controls (n ¼ 9) aged 7 months--5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP). RESULTS: There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean±s.d.: 22.6±12.5 vs 1.97±0.79 ng mlÀ1, P ¼ 0.005), and PP levels were significantly lower (22.6±12.5 vs 69.8±43.8 pmol lÀ1, Po0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects.
    [Show full text]
  • Role of Leptin in Inflammation and Vice Versa
    International Journal of Molecular Sciences Review Role of Leptin in Inflammation and Vice Versa Antonio Pérez-Pérez *, Flora Sánchez-Jiménez, Teresa Vilariño-García and Víctor Sánchez-Margalet * Department of Medical Biochemistry and Molecular Biology, and Immunology, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain; [email protected] (F.S.-J.); [email protected] (T.V.-G.) * Correspondence: [email protected] (A.P.-P.); [email protected] (V.S.-M.) Received: 16 July 2020; Accepted: 14 August 2020; Published: 16 August 2020 Abstract: Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity.
    [Show full text]
  • Selective Interaction Between Leptin and Insulin Signaling Pathways in a Hepatic Cell Line
    Selective interaction between leptin and insulin signaling pathways in a hepatic cell line Ildiko Szanto and C. Ronald Kahn* Joslin Diabetes Center, Research Division and Department of Medicine, Harvard Medical School, Boston, MA 02215 Contributed by C. Ronald Kahn, December 29, 1999 Leptin is a 16-kDa hormone secreted by adipocytes and plays an enzymes, glucokinase and phosphoenolpyruvate carboxykinase important role in control of feeding behavior and energy expen- (PEPCK; refs. 12 and 13). diture. In obesity, circulating levels of leptin and insulin are high Direct cross talk between the leptin and insulin signaling because of the presence of increased body fat mass and insulin systems in in vitro systems remains unclear. In HepG2 human resistance. Recent reports have suggested that leptin can act hepatoma cells, leptin antagonizes insulin-induced down- through some of the components of the insulin signaling cascade, regulation of PEPCK expression and decreases insulin- such as insulin receptor substrates (IRS-1 and IRS-2), phosphatidyl- stimulated tyrosine phosphorylation of IRS-1 but enhances inositol 3-kinase (PI 3-kinase), and mitogen-activated protein ki- IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) nase, and can modify insulin-induced changes in gene expression activity (14); in C2C12 cells, leptin stimulates a non-IRS-1- in vitro and in vivo. Well differentiated hepatoma cells (Fao) associated PI 3-kinase and mimics insulin action on glucose possess both the long and short forms of the leptin receptor and transport and glycogen synthesis (15). In OB-RL-transfected respond to leptin with a stimulation of c-fos gene expression.
    [Show full text]
  • Leptin-To-Adiponectin Ratio As a Potential Atherogenic Index in Obese Type 2 Diabetic Patients
    BRIEF REPORT Leptin-to-Adiponectin Ratio as a Potential Atherogenic Index in Obese Type 2 Diabetic Patients 1 3 NORIKO SATOH, MD, PHD KAZUNORI YAMADA, MD, PHD written informed consent. The patients 1 3 MITSUHIDE NARUSE, MD, PHD HIDESHI KUZUYA, MD, PHD had stable and relatively high blood glu- 1 1 TAKESHI USUI, MD, PHD AKIRA SHIMATSU, MD, PHD cose and HbA levels (7.0% Յ HbA Յ 1 2,4 1c 1c TETSUYA TAGAMI, MD, PHD YOSHIHIRO OGAWA, MD, PHD 2 9.0%). They were classified by BMI TAKAYOSHI SUGANAMI, MD, PHD (nonobese BMI Ͻ25.0 and obese BMI Ն25.0 kg/m2, according to the criteria of the Japan Society for the Study of Obesity) (10); 98 and 60 were defined as nonobese besity promotes the progression of vascular remodeling and neointimal for- and obese subjects, respectively. There atherosclerosis by inducing multi- mation are markedly attenuated in leptin- were 39 men and 59 women in the non- O ple cardiovascular and metabolic deficient ob/ob mice and db/db mice with obese group and 30 men and 30 women derangements such as diabetes, hyperten- leptin receptor mutation (6,7), suggesting in the obese group. None were receiving sion, and dyslipidemia, all of which have that leptin may accelerate the develop- insulin, metformin, or thiazolidinedio- high atherogenic potential. Adipose tissue ment of vascular injury. Conversely, stud- nes. Fifty-one nonobese and 25 obese has been considered an important endo- ies with adiponectin-deficient mice have subjects had been treated with sulfonyl- crine organ that secretes many biologi- revealed that adiponectin plays a protec- ureas, whereas 47 and 35, respectively, cally active substances, collectively tive role in the development of atheroscle- had only been treated with diet.
    [Show full text]
  • Alterations in Adiponectin, Leptin, Resistin, Testosterone, and Cortisol Across Eleven Weeks of Training Among Division One Collegiate Throwers: a Preliminary Study
    Journal of Functional Morphology and Kinesiology Brief Report Alterations in Adiponectin, Leptin, Resistin, Testosterone, and Cortisol across Eleven Weeks of Training among Division One Collegiate Throwers: A Preliminary Study W. Guy Hornsby 1,* , G. Gregory Haff 2 , Dylan G. Suarez 3 , Michael W. Ramsey 3, N. Travis Triplett 4, Justin P. Hardee 5 , Margaret E. Stone 3 and Michael H. Stone 3 1 College of Physical Activity and Sport Sciences, West Virginia University, Morgantown, WV 26505, USA 2 School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia; g.haff@ecu.edu.au 3 Center of Excellence for Sport Science and Coach Education, East Tennessee State University, Johnson City, TN 37614, USA; [email protected] (D.G.S.); [email protected] (M.W.R.); [email protected] (M.E.S.); [email protected] (M.H.S.) 4 Department of Health and Exercise Science, Appalachian State University Boone, NC 28607, USA; [email protected] 5 Centre for Muscle Research, Department of Physiology, University of Melbourne, Victoria 3010, Australia; [email protected] * Correspondence: [email protected]; Tel.: +1-304-293-0851 Received: 19 May 2020; Accepted: 18 June 2020; Published: 19 June 2020 Abstract: Cytokine and hormone concentrations can be linked to the manipulation of training variables and to subsequent alterations in performance. Subjects: Nine D-1 collegiate throwers and 4 control subjects participated in this preliminary and exploratory report. Methods: Hormone (testosterone (T) and cortisol (C)) and adipokine (adiponectin, leptin, and resistin) measurements were taken at weeks 1, 7, and 11 for the throwers and weeks 1 and 11 for the control group.
    [Show full text]
  • Peptide YY (PYY)3–36 Modulates Thyrotropin Secretion in Rats
    459 Peptide YY (PYY)3–36 modulates thyrotropin secretion in rats K J Oliveira, G S M Paula, R H Costa-e-Sousa, L L Souza, D C Moraes, F H Curty and C C Pazos-Moura Laborato´rio de Endocrinologia Molecular, Instituto de Biofı´sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21949-900, Brazil (Requests for offprints should be addressed to C C Pazos-Moura; Email: [email protected]) Abstract Peptide YY (PYY)3-36 is a gut-derived hormone, with a However, in fasted rats, PYY3-36 at both doses elicited a proposed role in central mediation of postprandial satiety signals, significant rise (approximately twofold increase, P!0.05) in as well as in long-term energy balance. In addition, recently,the serum TSH observed 15 min after the hormone injection. ability of the hormone to regulate gonadotropin secretion, PYY3-36 treatment did not modify significantly serum T4,T3,or acting at pituitary and at hypothalamus has been reported. Here, leptin. Therefore, in the present paper, we have demonstrated we examined PYY3-36 effects on thyrotropin (TSH) secretion, that the gut hormone PYY3-36 acts directly on the pituitary both in vitro and in vivo.PYY3-36-incubated rat pituitary glands gland to inhibit TSH release, and in the fasting situation, in vivo, showed a dose-dependent decrease in TSH release, with 44 and when serum PYY3-36 is reduced, the activity of thyroid axis is K K 62% reduction at 10 8 and 10 6 M(P!0.05 and P!0.001 reduced as well.
    [Show full text]