scholarly journals Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

2021 ◽  
Author(s):  
Kengo Inada ◽  
Kazuko Tsujimoto ◽  
Masahide Yoshida ◽  
Katsuhiko Nishimori ◽  
Kazunari Miyamichi
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Neural Circuit ◽  
Intraperitoneal Administration ◽  
Whole Body ◽  
Hypothalamic Nucleus ◽  
Physiological Regulation ◽  
Hypothalamic Regulation ◽  
Obesity In Mice ◽  
Anorexigenic Effect

Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (OT) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. OT has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of OT signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of OT or OT receptor (OTR) has little effect on food intake. We herein show that acute conditional KO (cKO) of OT selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of OT rescues the hyperphagic phenotype of the PVH OT cKO model. Furthermore, we show that cKO of OTR selectively in the posterior hypothalamic regions, which include the primary centers for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data functionally reveal that OT signaling in the posterior hypothalamic regions suppresses excessive food intake.

scholarly journals Regulation of food intake and body weight by recombinant proghrelin

2009 ◽  
Vol 297 (6) ◽  
pp. E1269-E1275 ◽  
Author(s):  
Weizhen Zhang ◽  
Arundhati Majumder ◽  
Xiaobin Wu ◽  
Michael W. Mulholland
Keyword(s):  
Body Weight ◽  
Amino Acid ◽  
Energy Metabolism ◽  
Food Intake ◽  
Normal Saline ◽  
Biological Function ◽  
Intraperitoneal Administration ◽  
Fat Consumption ◽  
Regulate Food Intake ◽  
Cumulative Food Intake

Ghrelin is a 28-amino-acid hormone derived from the endoproteolytic processing of its prehormone proghrelin. Although ghrelin has been reported to regulate food intake and body weight, it is still unknown whether proghrelin exercises any biological function. Here we show that recombinant proghrelin alters food intake and energy metabolism in mice. After intraperitoneal administration of recombinant proghrelin (100 nmol/kg body wt), cumulative food intake was significantly increased at days 1, 2, and 3 (6 ± 0.3, 13 ± 0.5, and 20 ± 0.8 g vs. 5 ± 0.2, 10 ± 0.2, and 16 ± 0.3 g of the control mice receiving normal saline, respectively, n = 6, P < 0.05). Twelve-hour cumulative food intake in the light photo period in mice treated with proghrelin increased significantly relative to the control (2.1 ± 0.04 vs. 1.3 ± 0.2 g, n = 6, P < 0.05). No change in 12-h cumulative food intake in the dark photo period was observed between mice treated with proghrelin and vehicle (4.2 ± 0.6 vs. 4.3 ± 0.6 g, n = 6, P > 0.05). This is associated with a decrease in body weight (0.42 ± 0.04 g) for mice treated with proghrelin, whereas control animals gained body weight (0.31 ± 0.04 g). Mice treated with proghrelin demonstrate a significant decrease in respiratory quotient, indicating an increase in fat consumption. Recombinant proghrelin is functionally active with effects on food intake and energy metabolism.

Total Body Potassium and Body Fat Estimation in Relationship to Height, Sex, Age, Malnutrition and Obesity

1975 ◽  
Vol 48 (5) ◽  
pp. 431-440 ◽  
Author(s):  
C. J. Edmonds ◽  
B. M. Jasani ◽  
T. Smith
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Fat Free Mass ◽  
Whole Body ◽  
Regression Equations ◽  
Total Body Potassium ◽  
Normal Individuals ◽  
Males And Females ◽  
Total Body

1. Total body potassium was estimated by 40K measurement with a high-sensitivity whole-body counter in normal individuals over a wide age range and in patients who were obese or were grossly wasted as a result of various conditions which restricted food intake. 2. Potassium concentration (mmol/kg body weight) fell with increasing age over 30 years in both normal males and females, but when individuals of different age groups were matched for height, a significant fall in total body potassium with increasing age was observed only in males. Total body potassium of females was about 75% that of males of similar height when young, the sex difference decreasing with ageing. In the normal population, total body potassium was significantly correlated with height and with weight; regression equations for various relationships are given. 3. Fat-free mass was estimated from total body potassium, values of 65 and 56 mmol of potassium/kg fat-free mass being used for males and females respectively. Body fat estimated by this method correlated well with skinfold measurements over a wide range of body weight but in malnourished individuals having inadequate food intake there was considerable discrepancy and present formulae for estimating fat-free mass from total body potassium appear unsatisfactory in malnutrition. Considerable differences between expected and observed values of total body potassium were found in muscular individuals and in normal individuals who were thin but whose body weight was relatively constant. 4. The patients with malnutrition were low both in body fat as estimated by skinfold thickness and in total body potassium estimated on the basis of height. Plasma potassium was, however, normal and potassium supplements did not increase the total body potassium. 5. Total body potassium of obese individuals was not significantly different from that of normal weight individuals on the basis of height. Total body potassium fell on weight reduction with a very low energy diet of 1260 kJ (300 kcal.) daily but changed little with a 3300 kJ (800 kcal.) diet over several months' observation. 6. For overweight, obese individuals, total body potassium was best predicted from the individual's height. For those whose body weight was less than expected, the use of weight gave the best prediction but the error was considerable when the weight deviation was large.

scholarly journals Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

Cell Reports ◽  
2017 ◽  
Vol 19 (11) ◽  
pp. 2202-2209 ◽  
Author(s):  
Saira Hameed ◽  
Michael Patterson ◽  
Waljit S. Dhillo ◽  
Sofia A. Rahman ◽  
Yue Ma ◽  
...  
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Food Intake ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Ventromedial Hypothalamus ◽  
Physiological Regulation ◽  
Receptor Beta

scholarly journals Corticotropin-Releasing Hormone-Mediated Pathway of Leptin to Regulate Feeding, Adiposity, and Uncoupling Protein Expression in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3547-3554 ◽  
Author(s):  
Takayuki Masaki ◽  
Go Yoshimichi ◽  
Seiichi Chiba ◽  
Tohru Yasuda ◽  
Hitoshi Noguchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Mrna Expression ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Hypothalamic Nucleus ◽  
Fat Cell ◽  
Brown Adipose

Abstract To examine the functional role of CRH in the regulation of energy homeostasis by leptin, we measured the effects of the CRH antagonist, α-helical CRH 8–41 (αCRH) on a number of factors affected by leptin activity. These included food intake, body weight, hypothalamic c-fos-like immunoreactivity (c-FLI), weight and histological characterization of white adipose tissue, and mRNA expressions of uncoupling protein (UCP) in brown adipose tissue (BAT) in C57Bl/6 mice. Central infusion of leptin into the lateral cerebroventricle (icv) caused significant induction of c-FLI in the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus, and arcuate nucleus. In all these nuclei, the effect of leptin on expression of cFLI in the PVN and VMH was decreased by treatment with αCRH. Administration of leptin markedly decreased cumulative food intake and body weight with this effect being attenuated by pretreatment with αCRH. In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue. Those changes in BAT were also decreased by treatment with αCRH. As a consequence of the effects on food intake or energy expenditure, treatment with αCRH attenuated the leptin-induced reduction of body adiposity, fat cell size, triglyceride contents, and ob mRNA expression in white adipose tissue. Taken together, these results indicate that CRH neurons in the PVN and VMH may be an important mediator for leptin that contribute to regulation of feeding, adiposity, and UCP expression.

High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus

2014 ◽  
Vol 306 (1) ◽  
pp. R34-R44 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo Rorato ◽  
Ernane Torres Uchoa ◽  
Paula Marangon ◽  
Glauber S. F. da Silva ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Brain Stem ◽  
High Fat Diet ◽  
Control Diet ◽  
Body Weight Loss ◽  
Hypothalamic Nucleus ◽  
High Fat

Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.

scholarly journals Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight

2008 ◽  
Vol 294 (2) ◽  
pp. R352-R361 ◽  
Author(s):  
Susan Aja ◽  
Leslie E. Landree ◽  
Amy M. Kleman ◽  
Susan M. Medghalchi ◽  
Aravinda Vadlamudi ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fatty Acid ◽  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Fatty Acid Synthase ◽  
Intraperitoneal Administration ◽  
Carnitine Palmitoyl Transferase ◽  
Dose Dependent

Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1–56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.

scholarly journals Some biological aspects of partial starvation. The effect of weight loss and regrowth on body compsition in sheep

1974 ◽  
Vol 32 (3) ◽  
pp. 515-527 ◽  
Author(s):  
J. H. Burton ◽  
M. Anderson ◽  
J. T. Reid
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gastrointestinal Tract ◽  
Food Intake ◽  
Energy Content ◽  
Normal Growth ◽  
Whole Body ◽  
Tissue Samples ◽  
Fat Depots ◽  
Dietary Treatments

1. A study of the effects of four dietary treatments on body-weight and the water, protein, fat and energy content of the empty bodies of forty-three Suffolk ewes is reported. The treatments were as follows: T1, ad lib. food intake from a full-body-weight (FBW) of 40 kg to 71 kg; T2, partial fasting with a resulting weight loss from 71 kg to 50 kg FBW; T3, realimentation and regrowth from 50 kg to 71 kg FBW; T4, a slight food restriction producing a reduced growth rate from 40 kg to 50 kg FBW followed by ad lib. food intake from 50 kg to 71 kg FBW. On all treatments sheep were slaughtered in groups of three at 7 kg intervals between 50 kg and 71 kg FBW.2. The whole body, with the exception of several body organs and glands, wool and the contents of the gastrointestinal tract, was minced and analysed for water, protein, fat and energy. Adipose tissue samples were removed at slaughter from subcutaneous and internal fat depots for histological examination. Regression analysis was used in comparing treatment effects on body composition.3. No significant differences were observed between the results of T1 and T4. In consequence these results were pooled and are referred to as T1. At 40 kg FBW the empty (ingesta-free) bodies of the lambs contained approximately 52% water, 14 % protein and 29% fat. Through normal growth to 71 kg FBW on T1 these values had changed to 40, 11.5 and 45 %, respectively. Following weight loss to 50 kg FBW on T2 the water, protein and fat contents of the empty bodies were 47, 13.5 and 35 %, respectively. Regrowth on T3 to 71 kg FBW resulted in little change in these components, the respective values being 46, 13 and 36 %. The sheep which had undergone weight loss and regrowth retained significantly more water and less energy than normally grown controls and tended to deposit less fat and more protein.4. Gastrointestinal tract contents accounted for 11 % of FBW at 71 kg in T3 animals. In T1, the value was 7.1 % at a similar FBW. Thus there was an average increase of over 56 % in contents in the realimented animals.5. Mean adipocyte diameter at 50 kg FBW on T1 was 134 ± 3 μm. At 71 kg FBW the mean diameter had increased to 152 ± 9 μm. Weight reduction (T2) and regrowth (T3) resulted in mean diameters of 122 ± 4 μm and 143 ± 4 μm at 50 kg and 71 kg FBW, respectively.

CONTINUOUS METABOLIC STUDIES ON NORMAL AND DEPANCREATIZED DOGS DURING REPEATED WHOLE BODY X IRRADIATION

1961 ◽  
Vol 39 (5) ◽  
pp. 863-871
Author(s):  
O. H. Gaehler ◽  
R. J. Bloor ◽  
Harold C. Choitz
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Food Intake ◽  
Urine Volume ◽  
Insulin Requirement ◽  
Metabolic Effects ◽  
Whole Body ◽  
Total Dosage ◽  
X Irradiation ◽  
Main Portion

Experiments on normal and depancreatized bitches were carried out to determine how well multiple doses of 90 r or less of X radiation are tolerated, and whether there are any metabolic effects suggesting stimulation or suppression of the adrenals. In two normal animals, total dosage for the main portion of the trunk was 574 and 3549 r, in 4 and 22 months, respectively; in the depancreatized one, 807 r in 9 months. Dosages for head and pelvis approximated 44% of these amounts. Food intake was constant, and daily records were kept of body weight, water intake, urine volume, and urine nitrogen. The general condition of all animals remained excellent. Periods of estrus continued. Weight was maintained or increased during long series of exposures. No changes in water balance or nitrogen output occurred which resembled those observed in dogs receiving corticotropin or hydrocortisone (1). In the depancreatized animal, the insulin requirement, known for 5 preceding years, was unaffected. Thus no evidence for stimulation or suppression of adrenal function was obtained. Histological examination of bone marrow and other tissues of the animal which received the largest total dose gave little evidence of damage. Moderate increases in urine volume of the normal animals suggested possible early renal impairment.

scholarly journals Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons

2013 ◽  
Vol 305 (4) ◽  
pp. R359-R368 ◽  
Author(s):  
Jussara M. do Carmo ◽  
Alexandre A. da Silva ◽  
John S. Rushing ◽  
Benjamin Pace ◽  
John E. Hall
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Food Intake ◽  
Acute Stress ◽  
Whole Body ◽  
The Right ◽  
Differential Control ◽  
Cardiovascular Functions

We examined the role of melanocortin-4 receptors (MC4R) in proopiomelanocortin (Pomc) neurons in regulating metabolic and cardiovascular functions. Using Cre-loxP technology, we selectively rescued MC4R in Pomc neurons of mice with whole body MC4R deficiency (MC4R-Pomc-Cre mice). Body weight, food intake, and whole body oxygen consumption (V̇o2) were determined daily, and blood pressure (BP), heart rate (HR), and body temperature were measured 24 h/day by telemetry. An intracerebroventricular cannula was placed in the right lateral ventricle for intracerebroventricular infusions. Littermate MC4R-deficient (LoxTB-MC4R) mice were used as controls. After control measurements, the MC4R antagonist (SHU-9119; 1 nmol/h) was infused intracerebroventricularly for 7 days. Compared with LoxTB-MC4R mice, MC4R-Pomc-Cre mice were less obese (47 ± 2 vs. 52 ± 2 g) and had increased energy expenditure (2,174 ± 98 vs. 1,990 ± 68 ml·kg−1·min−1), but food intake (4.4 ± 0.2 vs. 4.3 ± 0.3 g/day), BP (112 ± 1 vs. 109 ± 3 mmHg), and HR [557 ± 9 vs. 551 ± 14 beats per minute (bpm)] were similar between groups. Chronic SHU-9119 infusion increased food intake (4.2 ± 0.2 to 6.1 ± 0.5 g/day) and body weight (47 ± 2 to 52 ± 2 g) in MC4R-Pomc-Cre mice, while no changes were observed in LoxTB-MC4R mice. Chronic SHU-9119 infusion also increased BP and HR by 5 ± 1 mmHg and 60 ± 8 bpm in MC4R-Pomc-Cre mice without altering BP or HR in LoxTB-MC4R mice. These results indicate that MC4Rs in Pomc neurons are important for regulation of energy balance. In contrast, while activation of MC4R in Pomc neurons facilitates the BP response to acute stress, our data do not support a major role of MC4R in Pomc neurons in regulating baseline BP and HR.

Sign in / Sign up

Export Citation Format

Share Document