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 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.

The dare gene: steroid hormone production, olfactory behavior, and neural degeneration in Drosophila

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4591-4602 ◽  
Author(s):  
M.R. Freeman ◽  
A. Dobritsa ◽  
P. Gaines ◽  
W.A. Segraves ◽  
J.R. Carlson
Keyword(s):  
Nervous System ◽  
Steroid Hormones ◽  
Steroid Hormone ◽  
Larval Instar ◽  
Hormone Production ◽  
Ring Gland ◽  
Olfactory Stimuli ◽  
Steroid Hormone Signaling ◽  
Adrenodoxin Reductase ◽  
Strength Result

Steroid hormones mediate a wide variety of developmental and physiological events in insects, yet little is known about the genetics of insect steroid hormone biosynthesis. Here we describe the Drosophila dare gene, which encodes adrenodoxin reductase (AR). In mammals, AR plays a key role in the synthesis of all steroid hormones. Null mutants of dare undergo developmental arrest during the second larval instar or at the second larval molt, and dare mutants of intermediate severity are delayed in pupariation. These defects are rescued to a high degree by feeding mutant larvae the insect steroid hormone 20-hydroxyecdysone. These data, together with the abundant expression of dare in the two principal steroid biosynthetic tissues, the ring gland and the ovary, argue strongly for a role of dare in steroid hormone production. dare is the first Drosophila gene shown to encode a defined component of the steroid hormone biosynthetic cascade and therefore provides a new tool for the analysis of steroid hormone function. We have explored its role in the adult nervous system and found two striking phenotypes not previously described in mutants affected in steroid hormone signaling. First, we show that mild reductions of dare expression cause abnormal behavioral responses to olfactory stimuli, indicating a requirement for dare in sensory behavior. Then we show that dare mutations of intermediate strength result in rapid, widespread degeneration of the adult nervous system.

scholarly journals Energy homeostasis in apolipoprotein AIV and cholecystokinin-deficient mice

2017 ◽  
Vol 313 (5) ◽  
pp. R535-R548 ◽  
Author(s):  
Jonathan Weng ◽  
Danwen Lou ◽  
Stephen C. Benoit ◽  
Natalie Coschigano ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Fat Mass ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Lipid Transport ◽  
Fat Absorption ◽  
High Fat ◽  
Reduced Body ◽  
Brown Adipose

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.

scholarly journals Reduced Body Weight and Increased Postimplantation Fetal Death in Tyrosylprotein Sulfotransferase-1-deficient Mice

2002 ◽  
Vol 277 (26) ◽  
pp. 23781-23787 ◽  
Author(s):  
Ying-Bin Ouyang ◽  
James T. B. Crawley ◽  
Christopher E. Aston ◽  
Kevin L. Moore
Keyword(s):  
Body Weight ◽  
Fetal Death ◽  
Reduced Body ◽  
Deficient Mice

scholarly journals Inhibition of Sam68 triggers adipose tissue browning

2015 ◽  
Vol 225 (3) ◽  
pp. 181-189 ◽  
Author(s):  
Junlan Zhou ◽  
Min Cheng ◽  
Chan Boriboun ◽  
Mariam M Ardehali ◽  
Changfei Jiang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Acid Oxidation ◽  
M2 Macrophage ◽  
Fat Depots ◽  
Reduced Body ◽  
Brown Adipose ◽  
The Difference

Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders.

scholarly journals Models of energy homeostasis in response to maintenance of reduced body weight

Obesity ◽  
2016 ◽  
Vol 24 (8) ◽  
pp. 1620-1629 ◽  
Author(s):  
Michael Rosenbaum ◽  
Rudolph L. Leibel
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Reduced Body

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 MON-637 DREADD-Induced POMCARCNeuron Activation Increases Fasting Plasma Glucose Levels Through Changes in Hepatic Gluconeogenic Gene Expression but Not Changes in the HPA Axis Activity

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luane da Guia Vieira ◽  
Alan Carlos Fernandes ◽  
Tais Nascimento ◽  
Suzelei de Castro França ◽  
Jose Antunes-Rodrigues ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Hpa Axis ◽  
Plasma Glucose ◽  
Energy Homeostasis ◽  
Body Weight Loss ◽  
Reduced Body ◽  
Hpa Axis Activity

Abstract POMC neurons expressed in the ARC are essential for energy balance and glucose homeostasis. It has been suggested the involvement of these neurons in the control of endocrine axes, such as the HPA. During fasting, POMCARC neurons are silenced as an effort to reduce body weight loss and to avoid hypoglycemia. During this process glucocorticoid secretion and activation of enzymes involved in the hepatic gluconeogenesis take place in order to preserve the homeostasis. In this study, to clarify the contribution of POMCARC neurons to the adaptive changes in energy homeostasis, glucose metabolism and HPA axis activity induced by food deprivation we used DREADDs to specifically activate POMCARC. Bilateral injections of the AAV carrying the excitatory DREADD (hM3DGq) or only the reporter gene (mCherry) have been performed into the ARC of Pomc-ires-cre and WT mice. Two weeks later the animals were fasted for 36hr, treated with saline (5 i.p. injections each 8hrs) and blood samples were collected from the facial vein at 10am. Two weeks apart, the same animals were submitted to another period of fasting and treated with CNO (1mg/Kg, 5 i.p. injections each 8hrs). Four hours after the last injection of CNO, the mice were anesthetized, blood and the liver were collected and then the animals perfused for brain harvesting. Body weight measurements have been performed before and after the 36hrs period of fasting. Another set of Pomc-ires-cre (hM3DGq or mCherry) and WT animals were fasted (36hrs), treated with CNO (5X) and subjected to GTT. DREADD–induced activation of POMCARC neurons has been confirmed by the increased cFos/mCherry expression after CNO treatment only in Pomc-ires-cre animals expressing hM3DGq. We observed that the specific activation of POMCARC neurons did not change the fasting-induced activation of HPA axis. Surprisingly, we observed reduced body weight loss and higher plasma glucose in Pomc-ires-cre animals expressing the hM3DGq and treated with CNO. The GTT showed an impaired glucose tolerance after activation of POMCARC neurons. The increased fasting glucose plasma levels was associated with increased G6pc (Glucose-6-phosphatase) mRNA expression but with no effect on other hepatic gluconeogenic genes. The present study reveals that POMCARC neurons are not involved in the increased HPA axis activity in prolonged fasting conditions. Considering the classical anorexigenic/thermogenic and the glucose-lowering action of POMCARC neurons, the present data reveal an unpredicted reduced body weight loss and impaired glucose tolerance induced by activation of these neurons during fasting. These data reinforce the notion that POMCARC neurons are heterogeneous and might be playing dual effects on energy homeostasis. Of note, because part of ARC neurons shares a common progenitor, some of the functions ascribed to POMC neurons could be mediated by non-POMC neurons expressing the Cre transgene.

scholarly journals Body Composition, Insulin Resistance and Mediators of Appetite and Energy Homeostasis in Hyperthyroidism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A825-A825
Author(s):  
Avinash Patil ◽  
Suresh Vaikkakara ◽  
Alok Sachan ◽  
P Varma Buddharaju
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Body Weight ◽  
Fat Mass ◽  
Energy Homeostasis ◽  
The Body ◽  
Unexpected Finding ◽  
Reduced Body ◽  
Total Body ◽  
The Impact

Abstract Background: Hyperthyroidism is associated with reduced body weight despite an increase in appetite; due mainly to an increase in energy production. While appetite is regulated by the balance of orexogenic and anorexogenic peripheral signals like Ghrelin and Leptin respectively, energy expenditure is profoundly influenced by thyroxine itself as well as mediators like FGF 21 and Leptin. Hyperthyroidism offers a good model to study the impact of thyroid hormones on the above mediators. Materials & Methods: 35 adult patients with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, FGF21 levels & insulin resistance as well as the body composition by DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Results: Correction of hyperthyroidism was associated with an increase in body weight including both the lean body (p<0.001) and the fat mass (p<0.001), but with no change in percentage of total body fat (p=0.516). Accompanying the weight gain, there was no change in adiponectin (p=0.98), while a paradoxical decrease in insulin resistance was observed (p<0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 (p<0.001) and leptin levels (p=0.03) and an increase in ghrelin (p=0.05). Conclusion: Thyrotoxic state is associated with high leptin & FGF21 levels - both known to be thermogenic. Despite a lower weight and fat mass, thyrotoxicosis is associated with insulin resistance- possibly a direct effect of thyroxine. Ghrelin levels are low in thyrotoxicosis; which together with raised leptin is an unexpected finding, given the increased appetite observed in this condition.

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