Molecular and Phenotypic Analysis of Attractin Mutant Mice

Genetics ◽  
2001 ◽  
Vol 158 (4) ◽  
pp. 1683-1695 ◽  
Author(s):  
T M Gunn ◽  
T Inui ◽  
K Kitada ◽  
S Ito ◽  
K Wakamatsu ◽  
...  
Keyword(s):  
Body Weight ◽  
Mutant Mice ◽  
Compound Heterozygous ◽  
Phenotypic Analysis ◽  
Central Process ◽  
Molecular Abnormalities ◽  
Reduced Body ◽  
Pigment Type ◽  
The Central Nervous System ◽  
Relationship Of

Abstract Mutations of the mouse Attractin (Atrn; formerly mahogany) gene were originally recognized because they suppress Agouti pigment type switching. More recently, effects independent of Agouti have been recognized: mice homozygous for the Atrnmg-3J allele are resistant to diet-induced obesity and also develop abnormal myelination and vacuolation in the central nervous system. To better understand the pathophysiology and relationship of these pleiotropic effects, we further characterized the molecular abnormalities responsible for two additional Atrn alleles, Atrnmg and Atrnmg-L, and examined in parallel the phenotypes of homozygous and compound heterozygous animals. We find that the three alleles have similar effects on pigmentation and neurodegeneration, with a relative severity of Atrnmg-3J > Atrnmg > Atrnmg-L, which also corresponds to the effects of the three alleles on levels of normal Atrn mRNA. Animals homozygous for Atrnmg-3J or Atrnmg, but not Atrnmg-L, show reduced body weight, reduced adiposity, and increased locomotor activity, all in the presence of normal food intake. These results confirm that the mechanism responsible for the neuropathological alteration is a loss—rather than gain—of function, indicate that abnormal body weight in Atrn mutant mice is caused by a central process leading to increased energy expenditure, and demonstrate that pigmentation is more sensitive to levels of Atrn mRNA than are nonpigmentary phenotypes.

scholarly journals The ketogenic diet: a co-therapy in the treatment of mood disorders and obesity - a case report

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Agata Pieklik ◽  
Martyna Pawlaczyk ◽  
Joanna Rog ◽  
Hanna Karakuła-Juchnowicz
Keyword(s):  
Body Weight ◽  
Ketogenic Diet ◽  
Therapeutic Potential ◽  
Primary Source ◽  
Nutritional Intervention ◽  
Elevated Concentration ◽  
Body Weight Reduction ◽  
Reduced Body ◽  
The Central Nervous System

Abstract Introduction: There has been a growing interest in the ketogenic diet (KD) due to its suggested therapeutic potential to support numerous chronic diseases. KD is characterized by high amounts of fats and a reduced amount of carbohydrates and protein intake. During following the nutrition protocol, ketones are synthesised, which are the primary source of energy. The elevated concentration of ketones in blood serum inhibits hunger, what leads to reduced body weight. Some authors suggest KD has antidepressant potential and could stabilise mood by affecting neurotransmitters homeostasis in the central nervous system. Material and methods: The aim of the study was to assess the effect of KD on body weight reduction and improvement of mood in the patients with mood disorder diagnosis. To interpret the results of nutritional intervention, the laboratory parameters and structuralised scales and questionnaires were used. Results: After following 4-week therapy, the reduction of body weight, correction of some laboratory measurements and reduction in mood symptoms were noticed. Conclusions: The ketogenic diet affects the anthropometric measurements. However, a variety of simultaneous therapeutic approaches makes impossible determination of the effect on depressive symptoms.

scholarly journals Irisin deletion induces a decrease in growth and fertility in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yunyao Luo ◽  
Xiaoyong Qiao ◽  
Yaxian Ma ◽  
Hongxia Deng ◽  
Charles C. Xu ◽  
...  
Keyword(s):  
Body Weight ◽  
Steroid Hormones ◽  
Energy Homeostasis ◽  
Steroid Hormone ◽  
Mutant Mice ◽  
Sequencing Analysis ◽  
Hormone Production ◽  
Poor Growth ◽  
Reduced Body ◽  
Deficient Mice

Abstract Background Irisin, which is cleaved from fibronectin type III domain-containing protein 5 (Fndc5), plays an important role in energy homeostasis. The link between energy metabolism and reproduction is well known. However, the biological actions of irisin in reproduction remain largely unexplored. Methods In this study, we generated Fndc5 gene mutation to create irisin deficient mice. Female wild-type (WT) and Fndc5 mutant mice were fed with standard chow for 48 weeks. Firstly, the survival rate, body weight and fertility were described in mice. Secondly, the levels of steroid hormones in serum were measured by ELISA, and the estrus cycle and the appearance of follicles were determined by vaginal smears and ovarian continuous sections. Thirdly, mRNA-sequencing analysis was used to compare gene expression between the ovaries of Fndc5 mutant mice and those of WT mice. Finally, the effects of exogenous irisin on steroid hormone production was investigated in KGN cells. Results The mice lacking irisin presented increased mortality, reduced body weight and poor fertility. Analysis of sex hormones showed decreased levels of estradiol, follicle-stimulating hormone and luteinizing hormone, and elevated progesterone levels in Fndc5 mutant mice. Irisin deficiency in mice was associated with irregular estrus, reduced ratio of antral follicles. The expressions of Akr1c18, Mamld1, and Cyp19a1, which are involved in the synthesis of steroid hormones, were reduced in the ovaries of mutant mice. Exogenous irisin could promote the expression of Akr1c18, Mamld1, and Cyp19a1 in KGN cells, stimulating estradiol production and inhibiting progesterone secretion. Conclusions Irisin deficiency was related to disordered endocrinology metabolism in mice. The irisin deficient mice showed poor growth and development, and decreased fertility. Irisin likely have effects on the expressions of Akr1c18, Mamld1 and Cyp19a1 in ovary, regulating the steroid hormone production. This study provides novel insights into the potential role of irisin in mammalian growth and reproduction.

scholarly journals CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight

2017 ◽  
Vol 313 (3) ◽  
pp. E344-E358 ◽  
Author(s):  
Jennifer E. Richard ◽  
Lorena López-Ferreras ◽  
Belén Chanclón ◽  
Kim Eerola ◽  
Peter Micallef ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Insulin Release ◽  
Adrenergic Receptor ◽  
Metabolic Regulation ◽  
Receptor Activation ◽  
Reduced Body ◽  
The Central Nervous System ◽  
The Brain

Pharmacological β3-adrenergic receptor (β3AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as “browning”, and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β3AR agonists is mediated solely through activation of β3ARs in adipose tissue. However, β3ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β3ARs. Therefore, this study aimed to elucidate whether CNS β3ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β3AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β3AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β3AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β3AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β3AR activation.

scholarly journals NEURONAL FGF-21 SIGNALING: A SENSOR OF DIETARY PROTEIN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Cristal Hill ◽  
Christopher Morrison
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
Dietary Protein ◽  
Protein Restriction ◽  
Fibroblast Growth Factor 21 ◽  
Dietary Protein Restriction ◽  
Reduced Body ◽  
Low Protein ◽  
The Central Nervous System

Abstract Our data demonstrates that dietary protein restriction increases energy expenditure and improves glucose homeostasis, and that this effect is largely mediated by the metabolic hormone fibroblast growth factor 21(FGF21). Considering that the central nervous system (CNS) is acknowledged as a major regulator of both energy and glucose homeostasis, we have extended our studies to identify the tissue site mediating these FGF21-dependent effects via dietary protein restriction. In this study, mice with dysfunctional FGF21-signaling in either the CNS or adipose tissue were fed a control or low protein (LP)-diet to assess changes in body weight and metabolic endpoints. Our data show that LP diet increased energy expenditure and reduced body weight in control littermates, but these effects were lost in mice bearing CNS-specific deletion of Klb. These data highlight a liver to brain FGF21-signal as the first known neuroendocrine mechanism to explain the coordinated metabolic changes induced by dietary protein restriction.

Effect of [Asu,]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma

1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  
Keyword(s):  
Body Weight ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Regular Insulin ◽  
Prolactin Release ◽  
Saline Administration ◽  
The Central Nervous System ◽  
Plasma Prl ◽  
Male Subjects

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

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 Generation and Characterization of dickkopf3 Mutant Mice

2006 ◽  
Vol 26 (6) ◽  
pp. 2317-2326 ◽  
Author(s):  
Ivan del Barco Barrantes ◽  
Ana Montero-Pedrazuela ◽  
Ana Guadaño-Ferraz ◽  
Maria-Jesus Obregon ◽  
Raquel Martinez de Mena ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Clinical Chemistry ◽  
Lung Ventilation ◽  
Immunoglobulin M ◽  
Mutant Mice ◽  
Phenotypic Analysis ◽  
Thyroid Hormone Metabolism ◽  
Hormone Binding Protein ◽  
Deficient Mice

ABSTRACT dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity.

scholarly journals The Role of Snack Choices, Body Weight Stereotypes and Smoking Behavior in Assessing Risk Factors for Adolescent Overweight and Obesity

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Elena Raptou
Keyword(s):  
Body Weight ◽  
Smoking Behavior ◽  
Negative Influence ◽  
Overweight And Obesity ◽  
Individual Level ◽  
Level Data ◽  
Prevention Interventions ◽  
Frequent Consumption ◽  
Adolescent Overweight ◽  
Relationship Of

This study investigated the relationship of behavioral factors, such as snack choices, obesity stereotypes and smoking with adolescents’ body weight. Individual-level data for 1254 Greek youths were selected via a formal questionnaire. Snack choices seem to be gender specific with girls showing a stronger preference for healthier snacks. Frequent consumption of high-calorie and more filling snacks was found to increase Body Mass Index (BMI) in both genders. Fruit/vegetable snacks were associated with lower body weight in females, whereas cereal/nut snacks had a negative influence in males’ BMI. The majority of participants expressed anti-fat attitudes and more boys than girls assigned positive attributes to lean peers. The endorsement of the thin-ideal was positively associated with the BMI of both adolescent boys and girls. This study also revealed that neglecting potential endogeneity issues can lead to biased estimates of smoking. Gender may be a crucial moderator of smoking–BMI relationships. Male smokers presented a higher obesity risk, whereas female smokers were more likely to be underweight. Nutrition professionals should pay attention to increase the acceptance of healthy snack options. Gender differences in the influence of weight stereotypes and smoking on BMI should be considered in order to enhance the efficacy of obesity prevention interventions.

scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

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