scholarly journals Fibroblast Growth Factor 21 (FGF21) Administration Sex-Specifically Affects Blood Insulin Levels and Liver Steatosis in Obese Ay Mice

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3440
Author(s):  
Elena Makarova ◽  
Antonina Kazantseva ◽  
Anastasia Dubinina ◽  
Elena Denisova ◽  
Tatiana Jakovleva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Food Intake ◽  
Liver Steatosis ◽  
Melanocortin Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Blood Insulin ◽  
Metabolic Characteristics ◽  
Hepatic Lipid Accumulation ◽  
Ay Mice

FGF21 is a promising candidate for treating obesity, diabetes, and NAFLD; however, some of its pharmacological effects are sex-specific in mice with the Ay mutation that evokes melanocortin receptor 4 blockade, obesity, and hepatosteatosis. This suggests that the ability of FGF21 to correct melanocortin obesity may depend on sex. This study compares FGF21 action on food intake, locomotor activity, gene expression, metabolic characteristics, and liver state in obese Ay males and females. Ay mice were administered FGF21 for seven days, and metabolic parameters and gene expression in different tissues were assessed. Placebo-treated females were more obese than males and had lower levels of blood insulin and liver triglycerides, and higher expression of genes for insulin signaling in the liver, white adipose tissue (WAT) and muscles, and pro-inflammatory cytokines in the liver. FGF21 administration did not affect body weight, and increased food intake, locomotor activity, expression of Fgf21 and Ucp1 in brown fat and genes related to lipolysis and insulin action in WAT regardless of sex; however, it decreased hyperinsulinemia and hepatic lipid accumulation and increased muscle expression of Cpt1 and Irs1 only in males. Thus, FGF21’s beneficial effects on metabolic disorders associated with melanocortin obesity are more pronounced in males.

Role of central melanocortins in endotoxin-induced anorexia

1999 ◽  
Vol 276 (3) ◽  
pp. R864-R871 ◽  
Author(s):  
Qin-Heng Huang ◽  
Victor J. Hruby ◽  
Jeffrey B. Tatro
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Melanocortin Receptor ◽  
Receptor Subtype ◽  
Microbial Infection ◽  
Melanocyte Stimulating Hormone ◽  
The Central Nervous System

Inflammation and microbial infection produce symptoms, including fever, anorexia, and hypoactivity, that are thought to be mediated by endogenous proinflammatory cytokines. Melanocortins are known to act centrally to suppress effects on fever and other sequelae of proinflammatory cytokine actions in the central nervous system, but the roles of melanocortins in anorexia and hypoactivity occurring during the acute phase response are unknown. The present study was designed to determine the effects of exogenous and endogenous α-melanocyte stimulating hormone (α-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to their effects on fever. Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 μg/kg ip), followed 30 min later by intracerebroventricular injection of either α-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food intake, locomotor activity, and body temperature (Tb) were monitored during the ensuing 24-h period. Each of two intracerebroventricular doses of α-MSH (30 and 300 ng) potentiated the suppressive effects of LPS on food intake and locomotion, despite the fact that the higher dose alleviated LPS-induced fever. In control rats that were not treated with LPS, only the higher dose of α-MSH significantly inhibited food intake, and Tband locomotor activity were unaffected. To assess the roles of endogenous central melanocortins, LPS-treated rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R blockade did not affect Tbor food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. Taken together, the results suggest that exogenous and endogenous melanocortins acting centrally exert divergent influences on different aspects of the acute phase response, suppressing LPS-induced fever but contributing to LPS-induced anorexia and hypoactivity.

scholarly journals Evidence for an Interaction between CB1 Cannabinoid and Melanocortin MCR-4 Receptors in Regulating Food Intake

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3224-3231 ◽  
Author(s):  
A. N. A. Verty ◽  
J. R. McFarlane ◽  
I. S. McGregor ◽  
P. E. Mallet
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Cb1 Receptor ◽  
Melanocortin Receptor ◽  
Cb1 Receptors ◽  
Melanocortin System ◽  
Sr 141716

Abstract Melanocortin receptor 4 (MCR4) and CB1 cannabinoid receptors independently modulate food intake. Although an interaction between the cannabinoid and melanocortin systems has been found in recovery from hemorrhagic shock, the interaction between these systems in modulating food intake has not yet been examined. The present study had two primary purposes: 1) to examine whether the cannabinoid and melanocortin systems act independently or synergistically in suppressing food intake; and 2) to determine the relative position of the CB1 receptors in the chain of control of food intake in relation to the melanocortin system. Rats were habituated to the test environment and injection procedure and then received intracerebroventicular injections of various combinations of the MCR4 receptor antagonist JKC-363, the CB1 receptor agonist Δ9-tetrahydrocannabinol, the MCR4 receptor agonist α-MSH, or the cannabinoid CB1 receptor antagonist SR 141716. Food intake and locomotor activity were then recorded for 120 min. When administrated alone, SR 141716 and α-MSH dose-dependently attenuated baseline feeding, whereas sub-anorectic doses of SR 141716 and α-MSH synergistically attenuated baseline feeding when combined. Δ9-Tetrahydrocannabinol-induced feeding was not blocked by α-MSH, whereas SR 141716 dose-dependently attenuated JKC-363-induced feeding. Locomotor activity was not significantly affected by any drug treatment, suggesting that the observed effects on feeding were not due to a nonspecific reduction in motivated behavior. These findings revealed a synergistic interaction between the cannabinoid and melanocortin systems in feeding behavior. These results further suggested that CB1 receptors are located downstream from melanocortin receptors and CB1 receptor signaling is necessary to prevent the melanocortin system from altering food intake.

scholarly journals SAT-603 Growth Hormone-Releasing Hormone (GHRH) Antagonists Stimulate Feeding in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sheila Leone ◽  
Lucia Recinella, PharmD ◽  
Annalisa Chiavaroli, PharmD ◽  
Giustino Orlando, PharmD ◽  
Claudio Ferrante, PharmD ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Body Weight ◽  
Locomotor Activity ◽  
Food Intake ◽  
Brown Fat ◽  
Growth Hormone Releasing Hormone ◽  
Antitumor Effects ◽  
Releasing Hormone ◽  
Fat Depots

Abstract Growth hormone-releasing hormone (GHRH) is a hypothalamic neuropeptide which stimulates the synthesis and secretion of growth hormone (GH) in pituitary gland. GHRH was also found to modulate food intake in mammals. MIA-690 is a synthetic GHRH antagonist of the Miami (MIA) series with potent antitumor effects. To date, its role in hypothalamic feeding modulation has not been evaluated. In the present study, we aimed to investigate the effects of chronic MIA-690 administration on feeding behavior, locomotor activity and hypothalamic dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), orexigenic peptides [agouti-related peptide (AgRP) and neuropeptide Y (NPY)] and anorexigenic peptides [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] activity. Adult C57/BL6 mice were treated daily for 4 weeks by subcutaneous administration of (5 µg) MIA-690 or vehicle solution. Food intake and body weight were recorded every 4 days throughout the study. Immediately after the last injection, locomotor activity in the home cage was recorded, and thereafter animals were sacrificed. Visceral, subcutaneous and brown fat depots were quickly excised and weighed. Hypothalamus was also dissected for evaluating gene expression of AgRP, NPY, CART and POMC by real-time reverse transcription polymerase chain reaction. In addition, hypothalamic DA, NE and 5-HT levels were measured by high performance liquid chromatography (HPLC) coupled to electrochemical detection. Our findings show that administration of MIA-690 increased food intake and body weight, without affecting locomotor activity. No difference was observed in visceral, subcutaneous and brown fat mass in animals treated with MIA-690 or vehicle. As for neuromodulatory effects, a significant increase of AgRP gene expression and NE levels, along with a reduction of 5-HT levels were found after MIA-690 treatment. On the other hand, we did not observe any alteration in NPY, POMC and CART gene expression, as well as DA levels, following MIA-690 administration. In conclusion, chronic peripheral administration of MIA-690 could play an orexigenic role paralleled by increased body weight. The stimulation of feeding could be mediated, at least in part, by increased AgRP gene expression and NE levels and decreased 5-HT levels, in the hypothalamus.

scholarly journals The Same Metabolic Response to FGF21 Administration in Male and Female Obese Mice Is Accompanied by Sex-Specific Changes in Adipose Tissue Gene Expression

2021 ◽  
Vol 22 (19) ◽  
pp. 10561
Author(s):  
Elena Makarova ◽  
Antonina Kazantseva ◽  
Anastasia Dubinina ◽  
Tatiana Jakovleva ◽  
Natalia Balybina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Response ◽  
Food Preferences ◽  
Blood Parameters ◽  
Fibroblast Growth Factor 21 ◽  
Blood Levels ◽  
Male And Female ◽  
Metabolic Characteristics ◽  
Glucose And Lipid Metabolism ◽  
Female Specific

The preference for high-calorie foods depends on sex and contributes to obesity development. Fibroblast growth factor 21 (FGF21) beneficially affects taste preferences and obesity, but its action has mainly been studied in males. The aim of this study was to compare the effects of FGF21 on food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with diet-induced obesity. Mice were injected with FGF21 or vehicle for 7 days. Body weight, choice between standard (SD) and high-fat (HFD) diets, blood parameters, and gene expression in white (WAT) and brown (BAT) adipose tissues, liver, muscles, and the hypothalamus were assessed. Compared to males, females had a greater preference for HFD; less WAT; lower levels of cholesterol, glucose, and insulin; and higher expression of Fgf21, Insr, Ppara, Pgc1, Acca and Accb in the liver and Dio2 in BAT. FGF21 administration decreased adiposity; blood levels of cholesterol, glucose, and insulin; hypothalamic Agrp expression, increased SD intake, decreased HFD intake independently of sex, and increased WAT expression of Pparg, Lpl and Lipe only in females. Thus, FGF21 administration beneficially affected mice of both sexes despite obesity-associated sex differences in metabolic characteristics, and it induced female-specific activation of gene expression in WAT.

scholarly journals PGC-1β-expressing POMC neurons mediate the effect of leptin on thermoregulation in the mouse

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julien Delezie ◽  
Jonathan F. Gill ◽  
Gesa Santos ◽  
Bettina Karrer-Cardel ◽  
Christoph Handschin
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Heat Dissipation ◽  
Core Body Temperature ◽  
Locomotor Behavior ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Brown Adipose

Abstract The arcuate nucleus (ARC) of the hypothalamus is a key regulator of food intake, brown adipose tissue (BAT) thermogenesis, and locomotor activity. Whole-body deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1β) disrupts mouse circadian locomotor activity and BAT-regulated thermogenesis, in association with altered gene expression at the central level. We examined whether PGC-1β expression in the ARC is required for proper energy balance and locomotor behavior by generating mice lacking the PGC-1β gene specifically in pro-opiomelanocortin (POMC) neurons. POMC neuron-specific deletion of PGC-1β did not impact locomotor behavior, food intake, body composition, energy fuel utilization and metabolic rate in fed, 24-h fasted and 24-h refed conditions. In contrast, in the fed state, deletion of PGC-1β in POMC cells elevated core body temperature during the nighttime period. Importantly, this higher body temperature is not associated with changes in BAT function and gene expression. Conversely, we provide evidence that mice lacking PGC-1β in POMC neurons are more sensitive to the effect of leptin on heat dissipation. Our data indicate that PGC-1β-expressing POMC neurons are part of a circuit controlling body temperature homeostasis and that PGC-1β function in these neurons is involved in the thermoregulatory effect of leptin.

FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens

2006 ◽  
Vol 291 (1) ◽  
pp. R138-R147 ◽  
Author(s):  
Sami Dridi ◽  
Cedric Ververken ◽  
F. Bradley Hillgartner ◽  
Arckens Lutgarde ◽  
Estel Van der Gucht ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Food Intake ◽  
Broiler Chickens ◽  
Fatty Acid Synthase ◽  
Ingestive Behavior ◽  
The Other ◽  
Melanocortin Receptor ◽  
Synthetic Analog ◽  
Mrna Levels

Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and its synthetic analog C75 are hypothesized to alter the metabolism of neurons in the hypothalamus that regulate ingestive behavior to cause a profound decrease of food intake and an increase in metabolic rate, leading to body weight loss. The bulk of data exclusively originates from mammals (rodents); however, such effects are currently lacking in nonmammalian species. We have, therefore, addressed this issue in broiler chickens because this species is selected for high growth rate and high food intake and is prone to obesity. First, we demonstrate that FAS messenger and protein are expressed in the hypothalamus of chickens. FAS immunoreactivity was detected in a number of brain regions, including the nucleus paraventricularis magnocellularis and the nucleus infundibuli hypothalami, the avian equivalent of the mammalian arcuate nucleus, suggesting that FAS may be involved in the regulation of food intake. Second, we show that hypothalamic FAS gene expression was significantly ( P < 0.05) decreased by overnight fasting similar to that in liver, indicating that hypothalamic FAS gene is regulated by energy status in chickens. Finally, to investigate the physiological consequences of in vivo inhibition of fatty acid synthesis on food intake, we administered cerulenin by intravenous injections (15 mg/kg) to 2-wk-old broiler chickens. Cerulenin administration significantly reduced food intake by 23 to 34% ( P < 0.05 to P < 0.0001) and downregulated FAS and melanocortin receptors 1, 4, and 5 gene expression ( P < 0.05). However, the known orexigenic (neuropeptide Y, agouti gene-related peptide, orexin, and orexin receptor) and anorexigenic (pro-opiomelanocortin and corticotropin-releasing hormone) neuropeptide mRNA levels remained unchanged after cerulenin treatment. These results suggest that the catabolic effect of cerulenin in chickens may be mediated through the melanocortin system rather than the other neuropeptides known to be involved in food intake regulation.

Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes

2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Food Intake ◽  
Experimental Model ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Control ◽  
The Body ◽  
Sprague Dawley ◽  
Guluronic Acid

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.

scholarly journals Glucokinase Regulates Reproductive Function, Glucocorticoid Secretion, Food Intake, and Hypothalamic Gene Expression

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1928-1932 ◽  
Author(s):  
Xue-jun Yang ◽  
Jason Mastaitis ◽  
Tooru Mizuno ◽  
Charles V. Mobbs
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Reproductive Function
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