scholarly journals A Comparative Study of the Central Effects of Specific Proopiomelancortin (POMC)-Derived Melanocortin Peptides on Food Intake and Body Weight in Pomc Null Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5940-5947 ◽  
Author(s):  
Y. C. Loraine Tung ◽  
Sarah J. Piper ◽  
Debra Yeung ◽  
Stephen O’Rahilly ◽  
Anthony P. Coll
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Lean Mass ◽  
Energy Homeostasis ◽  
Reduce Food Intake ◽  
Dark Cycle ◽  
Short Term ◽  
Reduced Body ◽  
Melanocortin Peptides ◽  
Anorexigenic Effect

Functional disruption of either MC3R or MC4R results in obesity, implicating both in the control of energy homeostasis. The ligands for these receptors are derived from the prohormone proopiomelancortin (POMC), which is posttranslationally processed to produce a set of melanocortin peptides with a range of activities at the MC3R and MC4R. The relative importance of each of these peptides α-MSH, γ3-MSH, γ2-MSH, γ-lipotropin (γ-LPH) and, in man but not in rodents, β-MSH] in the maintenance of energy homeostasis is, as yet, unclear. To investigate this further, equimolar amounts (2 nmol) of each peptide were centrally administered to freely feeding, corticosterone-supplemented, Pomc null (Pomc−/−) mice. After a single dose at the onset of the dark cycle, α-MSH had the most potent anorexigenic effect, reducing food intake to 35% of sham-treated animals. β-MSH, γ-LPH, and γ3- and γ2-MSH all reduced food intake but to a lesser degree. The effects of peptide administration over 3 d were also assessed. Only α-MSH significantly reduced body weight, affecting both fat and lean mass. Other peptides had no significant effect on body weight. Pair-feeding of sham-treated mice to those treated with α-MSH resulted in identical changes in total weight, fat and lean mass indicating that the effects of α-MSH were primarily due to reduced food intake rather than increased energy expenditure. Although other melanocortins can reduce food intake in the short-term, only α-MSH can reduce the excess fat and lean mass found in Pomc−/− mice, mediated largely through an effect on food intake.

scholarly journals Pancreatic signals controlling food intake; insulin, glucagon and amylin

2006 ◽  
Vol 361 (1471) ◽  
pp. 1219-1235 ◽  
Author(s):  
Stephen C Woods ◽  
Thomas A Lutz ◽  
Nori Geary ◽  
Wolfgang Langhans
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Endocrine Pancreas ◽  
Situational Factors ◽  
Meal Size ◽  
Vagus Nerves ◽  
Social Emotional ◽  
Short Term ◽  
The Brain

The control of food intake and body weight by the brain relies upon the detection and integration of signals reflecting energy stores and fluxes, and their interaction with many different inputs related to food palatability and gastrointestinal handling as well as social, emotional, circadian, habitual and other situational factors. This review focuses upon the role of hormones secreted by the endocrine pancreas: hormones, which individually and collectively influence food intake, with an emphasis upon insulin, glucagon and amylin. Insulin and amylin are co-secreted by B-cells and provide a signal that reflects both circulating energy in the form of glucose and stored energy in the form of visceral adipose tissue. Insulin acts directly at the liver to suppress the synthesis and secretion of glucose, and some plasma insulin is transported into the brain and especially the mediobasal hypothalamus where it elicits a net catabolic response, particularly reduced food intake and loss of body weight. Amylin reduces meal size by stimulating neurons in the hindbrain, and there is evidence that amylin additionally functions as an adiposity signal controlling body weight as well as meal size. Glucagon is secreted from A-cells and increases glucose secretion from the liver. Glucagon acts in the liver to reduce meal size, the signal being relayed to the brain via the vagus nerves. To summarize, hormones of the endocrine pancreas are collectively at the crossroads of many aspects of energy homeostasis. Glucagon and amylin act in the short term to reduce meal size, and insulin sensitizes the brain to short-term meal-generated satiety signals; and insulin and perhaps amylin as well act over longer intervals to modulate the amount of fat maintained and defended by the brain. Hormones of the endocrine pancreas interact with receptors at many points along the gut–brain axis, from the liver to the sensory vagus nerve to the hindbrain to the hypothalamus; and their signals are conveyed both neurally and humorally. Finally, their actions include gastrointestinal and metabolic as well as behavioural effects.

scholarly journals Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1–28 to Pomc−/− mice reduces food intake and weight but does not affect adrenal growth or corticosterone production

2006 ◽  
Vol 190 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Anthony P Coll ◽  
Martin Fassnacht ◽  
Steffen Klammer ◽  
Stephanie Hahner ◽  
Dominik M Schulte ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Reduce Food Intake ◽  
Appetite Control ◽  
Concurrent Administration ◽  
Physiological Level ◽  
Sham Treatment ◽  
Acth Treatment

Pro-opiomelanocortin (POMC) is a polypeptide precursor that undergoes extensive processing to yield a range of peptides with biologically diverse functions. POMC-derived ACTH is vital for normal adrenal function and the melanocortin α-MSH plays a key role in appetite control and energy homeostasis. However, the roles of peptide fragments derived from the highly conserved N-terminal region of POMC are less well characterized. We have used mice with a null mutation in the Pomc gene (Pomc−/−) to determine the in vivo effects of synthetic N-terminal 1–28 POMC, which has been shown previously to possess adrenal mitogenic activity. 1–28 POMC (20 μg) given s.c. for 10 days had no effect on the adrenal cortex of Pomc−/− mice, with resultant cortical morphology and plasma corticosterone levels being indistinguishable from sham treatment. Concurrent administration of 1–28 POMC and 1–24 ACTH (30 μg/day) resulted in changes identical to 1–24 ACTH treatment alone, which consisted of upregulation of steroidogenic enzymes, elevation of corticosterone levels, hypertrophy of the zona fasciculate, and regression of the X-zone. However, treatment of corticosterone-depleted Pomc−/− mice with 1–28 POMC reduced cumulative food intake and total body weight. These anorexigenic effects were ameliorated when the peptide was administered to Pomc−/− mice with circulating corticosterone restored either to a low physiological level by corticosterone-supplemented drinking water (CORT) or to a supraphysiological level by concurrent 1–24 ACTH administration. Further, i.c.v. administration of 1–28 POMC to CORT-treated Pomc−/− mice had no effect on food intake or body weight. In wild-type mice, the effects of 1–28 POMC upon food intake and body weight were identical to sham treatment, but 1–28 POMC was able to ameliorate the hyperphagia induced by concurrent 1–24 ACTH treatment. In a mouse model which lacks all endogenous POMC peptides, s.c. treatment with synthetic 1–28 POMC alone can reduce food intake and body weight, but has no impact upon adrenal growth or steroidogenesis.

scholarly journals Effects of estradiol and progesterone on food intake, body weight, and carcass adiposity in weanling rats

1981 ◽  
Vol 240 (5) ◽  
pp. E499-E503 ◽  
Author(s):  
S. M. Schwartz ◽  
G. N. Wade
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Reduce Food Intake ◽  
Reduced Body ◽  
Adipose Tissue Lipoprotein Lipase

The effects of estradiol and progesterone on food intake, body weight, carcass adiposity, and adipose tissue lipoprotein lipase (LPL) activity were investigated in weanling female rats. Treatment with estradiol benzoate (EB) reduced body weight gain in ovariectomized (OVX) weanlings as it does in adults. However, other responses to EB were attenuated or absent in weanlings. EB treatment did not reduce food intake, carcass adiposity, or adipose tissue LPL activity. This impaired responsiveness to EB may be due to decreased levels of cytoplasmic estrogen receptors in liver and adipose tissue (but not hypothalamus) in weanlings. On the other hand, responsiveness to progesterone was adultlike in weanlings. Treatment of OVX, EB-primed weanlings with progesterone increased food intake, body weight gain, and carcass adiposity. This adultlike responsiveness to progesterone was associated with adultlike levels of adipose tissue progestin receptors. However, progesterone treatment did not increase adipose tissue LPL activity in weanlings, indicating that changes in LPL activity are not necessary for progesterone-induced obesity.

scholarly journals MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity

2019 ◽  
Author(s):  
Tana S. Pottorf ◽  
Micaella Fagan ◽  
Bryan Burkey ◽  
David J. Cho ◽  
James E. Vath ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Mouse Model ◽  
Reduce Food Intake ◽  
Reduced Body ◽  
Conditional Deletion ◽  
Daily Food ◽  
Liver Morphology ◽  
Metabolic Indices ◽  
Preclinical And Clinical Studies

AbstractThe ciliopathies Bardet-Biedl Syndrome and Alström Syndrome are genetically inherited pleiotropic disorders with primary clinical features of hyperphagia and obesity. Methionine aminopeptidase 2 inhibitors (MetAP2i) have been shown in preclinical and clinical studies to reduce food intake, body weight, and adiposity. Here we investigated the effects of MetAP2i administration in a mouse model of ciliopathy produced by conditional deletion of the Thm1 gene in adulthood (Thm1 cko). Thm1 cko mice show decreased hypothalamic pro-opiomelanocortin expression as well as hyperphagia, obesity, metabolic disease and hepatic steatosis. In obese Thm1 cko mice, two-week administration of MetAP2i reduced daily food intake and reduced body weight 17.1% from baseline (vs. 5% reduction for vehicle). This was accompanied with decreased levels of blood glucose, insulin and leptin. Further, MetAP2i reduced gonadal adipose depots and adipocyte size and improved liver morphology. This is the first report of MetAP2i reducing hyperphagia and body weight, and ameliorating metabolic indices in a mouse model of ciliopathy. These results support further investigation of MetAP2 inhibition as a potential therapeutic strategy for ciliary-mediated forms of obesity.

scholarly journals Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Ishaq ◽  
Duyen Tran ◽  
Yijia Wu ◽  
Krzysztof Nowak ◽  
Bianca J. Deans ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Taste Perception ◽  
Chow Diet ◽  
Therapeutic Effects ◽  
Gustatory System ◽  
High Fat ◽  
Reduced Body

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Central Histamine, the H3-Receptor and Obesity Therapy

2019 ◽  
Vol 18 (7) ◽  
pp. 516-522
Author(s):  
Néstor F. Díaz ◽  
Héctor Flores-Herrera ◽  
Guadalupe García-López ◽  
Anayansi Molina-Hernández
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Receptor Ligands ◽  
Histaminergic System ◽  
H3 Receptor ◽  
Weight One ◽  
The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

scholarly journals Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPRmt in the hypothalamus of mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renata R. Braga ◽  
Barbara M. Crisol ◽  
Rafael S. Brícola ◽  
Marcella R. Sant’ana ◽  
Susana C. B. R. Nakandakari ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Body Weight ◽  
Physical Training ◽  
Energy Homeostasis ◽  
Mitochondrial Activity ◽  
In Vivo Experiments ◽  
Reduced Body ◽  
Hypothalamic Cells ◽  
Bxd Mice

AbstractThe maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPRmt) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPRmt in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPRmt markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPRmt in hypothalamic cells.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

scholarly journals COMPARISON EFFECT OF CV 12, ST 36 AND ST 40 EA ON SHORT TERM ENERGY BALANCE REGULATION IN HIGH FAT DIET RAT

2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Energy Balance ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Continuous Wave ◽  
Positive Control ◽  
Control Group ◽  
High Fat ◽  
Short Term

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.

scholarly journals Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 88 ◽  
Author(s):  
Mehdi Labyb ◽  
Chloé Chrétien ◽  
Aurélie Caillon ◽  
Françoise Rohner-Jeanrenaud ◽  
Jordi Altirriba
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Leptin Resistance ◽  
Obese Mice ◽  
Short Term ◽  
Continuous Administration ◽  
Pre Treatment ◽  
Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

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