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 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 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.

In Vivo Plasminogen Deficiency Reduces Fat Accumulation

2002 ◽  
Vol 87 (06) ◽  
pp. 1011-1019 ◽  
Author(s):  
Jill Ellis ◽  
Lawrence Yuen ◽  
Jane Hoover-Plow
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Whole Body ◽  
Glycerol Phosphate ◽  
Tissue Accumulation ◽  
Fat Depots ◽  
Reduced Body ◽  
Reduced Rate

SummaryObesity and non-insulin dependent diabetes are associated with a decrease in fibrinolysis, which is mediated by the plasminogen system. The purpose of the current study was to investigate the role of the plasminogen system in the reduced body weight of the plasminogen deficient (Plg−/−) mice. In this study we have found that the reduced body weight in Plg−/− mice is due to a reduced rate of the adipose tissue (25% less) and whole body fat (30% less) accumulation during growth in Plg−/− compared to wild-type (WT) littermates. When the mice are fed a high fat-lipogenic diet, adipose tissue accumulation increases in the Plg−/− mice indicating that the capacity for lipid filling of cells was not blocked. In addition, glycerol phosphate dehydrogenase, a marker of late differentiation, was not different in the depots from WT and Plg−/− mice. The number of stromal cells (number × 105/g adipose tissue), isolated from inguinal (Plg−/− 3.4 ± 1.2, n = 6; WT 0.17 ± 0.07, n = 7, p < 0.02) and gonadal (Plg−/− 11.0 ± 0.4, n = 6; WT 3.1 ± 0.7, n = 7, p < 0.05) fat depots, was markedly higher in the depots from the Plg−/− mice than WT mice. Differentiation of stromal cells in culture from the Plg−/− mice was reduced compared to cells from WT mice. These results suggest that differences in the stromal cell population are responsible for the reduced adipose tissue accumulation in the Plg−/− mice, and that the plasminogen system plays an important role in adipose tissue accumulation.

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 Role of SMAD2 and SMAD3 on Adipose Tissue Development and Function

2021 ◽  
Author(s):  
◽  
Roshan Kumari ◽  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Mass ◽  
Energy Homeostasis ◽  
Activin A ◽  
Male Mice ◽  
Proliferation And Differentiation

Introduction: Obesity and its associated metabolic syndrome are major medical problems worldwide including United States. Adipose tissue is the primary site of energy storage, playing important roles in health. Adipose tissue also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety, inflammation, and total energy homeostasis. Activin A and activin B play important roles in maintaining body composition and energy homeostasis. This dissertation highlights the role of activin/SMADs signaling in adipose tissue development, function, and maintenance. SMAD2/3 proteins are downstream mediators of transforming growth factor-β (TGFβ) family signaling, including activins, which regulate critical preadipocyte and mature adipocyte functions. Previous studies have demonstrated that Smad2 global knockout mice exhibit embryonic lethality, whereas global loss of Smad3 protects mice against diet-induced obesity and the direct contributions of Smad2 and Smad3 in adipose tissues individually or in combination and the responses of these tissues to activin signaling are unknown. Additionally, our lab demonstrated that the combined loss of activin A and activin B have reduced adiposity in mice and appearance of brown-like cells in visceral white adipose tissue. However, the cell-autonomous role of activins on cell proliferation and differentiation remained unknown in vitro. My hypothesis was that activin signaling regulate adipocyte differentiation and functions via SMAD2/3-mediated mechanism(s) and that the individual or combined adipose-specific deletion of SMAD2/SMAD3 would result in reduced adiposity similar to activin deficient mice. Objective: Here, we sought to determine the primary effects of adipocyte-selective reduction of Smad2 or Smad3 individually and in combination, on diet-induced adiposity and to establish whether preadipocytes isolated from subcutaneous and visceral white adipose tissues differ in their differentiation capacity. We also assessed the role of activins on cell proliferation and differentiation using an in vitro model. Research Design: To assess the adipose-selective requirements of Smad2, Smad3 and Smad2/3, we generated three lines of adipose-selective conditional knockout (cKO) mice including Smad2cKO, Smad3cKO, and Smad2/3 double cKO mice using Smad2 and/or Smad3 “floxed” mice intercrossed with Adiponectin-Cre mice. Additionally, we isolated preadipocytes and examined adipogenic activity of visceral and subcutaneous preadipocyte and the effects of activin on preadipocyte proliferation and differentiation in vitro. Furthermore, we used mouse embryonic fibroblasts (MEFs) from wild type mice and activin double knockout mice to study the cell autonomous role of activin on differentiation and cell fate. Results: Our results demonstrated that subcutaneous preadipocytes differentiate uniformly and almost all wildtype subcutaneous preadipocytes differentiated into mature adipocytes. In contrast, visceral preadipocytes differentiated poorly. Exogenous activin A promoted proliferation and suppressed differentiation of subcutaneous preadipocytes more robustly given that visceral adipocytes differentiate poorly at baseline. Additionally, global knockout of activin A and B promoted differentiation and browning in differentiated MEFs in vitro consistent with in vivo studies. Furthermore, we showed that Smad2cKO mice did not exhibit significant effects on weight gain, irrespective of diet, whereas Smad3cKO male mice displayed a trend of reduced body weight on high fat diet. On both (LFD and HFD) diets, Smad3cKO male mice displayed an adipose depot-selective phenotype, with significant reduction in subcutaneous fat mass but not visceral fat mass. Smad2/3cKO male mice did not show any difference in body weight or fat mass compared to control mice. Female mice with adipose-selective combined deletion of Smad2/3, displayed reduced body weight and reduction of fat mass in both visceral and subcutaneous depot with higher metabolic rate on HFD compared to control littermates. Conclusions: Our study demonstrated that Smad3 is an important contributor to the development and/or maintenance of subcutaneous white adipose tissue in a sex-selective fashion. Combined reduction of Smad2/3 protects female mice from diet induced obesity and is important for visceral and subcutaneous depots in a sex-selective fashion. These findings have implications for understanding SMAD-mediated, depot selective regulation of adipocyte growth and differentiation. Activin treatment promoted proliferation of preadipocytes, while activin deficiency promoted differentiation and altered the phenotypic characteristics of White adipocytes to brown-like cells in vitro consistent with in vivo.

scholarly journals Properties of a novel series of inhibitors of rumen methanogenesis; in vitro and in vivo experiments including growth trials on 2,4-bis (trichloromethyl)-benzo [1, 3]dioxin-6-carboxylic acid

1982 ◽  
Vol 47 (3) ◽  
pp. 565-576 ◽  
Author(s):  
A. Davies ◽  
H. N. Nwaonu ◽  
G. Stanier ◽  
F. T. Boyle
Keyword(s):  
Body Weight ◽  
Carboxylic Acid ◽  
Methane Production ◽  
Live Weight ◽  
Dietary Energy ◽  
In Vivo Experiments ◽  
Growth Trial ◽  
Concentrate Element

1. A procedure for measuring methane production by rumen contents incubated anaerobically in vitro is described. Assessments of methane production in vivo, in both sheep and cattle, were made by withdrawal of rumen contents and measuring their capacity to produce methane in vitro.2. Many members of a series of 6-substituted 2,4-bis (trichloromethyl)-benzo[1,3]dioxins were potent inhibitors of methanogenesis by rumen contents in vitro. The most potent compound inhibited methane production by 70% or more at a concentration of 1 μg/ml (approximately 2.5 μmol/l).3. Two compounds, namely the 6-carboxylic acid (IC1 13409) and the 6-carboxamide (ICI 43586), caused a large inhibition of methanogenesis sustained for many hours, following a single intrarumen injection in sheep or cattle. Inhibition was maintained for long periods by single daily dosing directly into the rumen or by dietary administration.4. In a 28-week growth trial in beef cattle inclusion of ICI 13409 in the concentrate element of the diet, at a level of 6 mg/kg body-weight, improved live-weight gam by 8·0% (P< 0·05) with respect to untreated animals whilst reducing food intake by 5·0% (P< 0·05). Smaller and not statistically-significant effects were seen with this compound at 3 mg/kg body-weight and with the antibiotic monensin(Romensin; ElancoPLC). All treatments significantly improved the retention of dietary energy into the carcass, offal and intestinal tracts of the trial animals and significantly reduced the quantity of methane eructed into expired gases.

scholarly journals Analysis of Animal Well-Being When Supplementing Drinking Water with Tramadol or Metamizole during Chronic Pancreatitis

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2306
Author(s):  
Guanglin Tang ◽  
Wiebke-Felicitas Nierath ◽  
Rupert Palme ◽  
Brigitte Vollmar ◽  
Dietmar Zechner
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Chronic Pancreatitis ◽  
Well Being ◽  
Nesting Behavior ◽  
Time Points ◽  
In Vivo Experiments ◽  
Distress Score ◽  
Burrowing Activity

Pain management during in vivo experiments is an animal welfare concern and is in many countries also legally required. In this study, we evaluated C57Bl/6J mice when 3 g/L metamizole or 1 g/L tramadol was provided via drinking water, before and during cerulein-induced chronic pancreatitis. Supplementation of drinking water with metamizole or tramadol did not significantly reduce the amount of consumed water. In order to evaluate the wellbeing of mice, a distress score, burrowing activity, nesting behavior, and body weight was assessed. Before induction of pancreatitis, neither tramadol nor metamizole influenced these readout parameters. Chronic pancreatitis caused a significantly increased distress score, decreased burrowing activity and a reduction in body weight. Mice drinking tramadol-supplemented water experienced less loss in body weight and consumed more water than mice drinking metamizole, at a few time-points during chronic pancreatitis. Pancreatic atrophy, a characteristic feature of chronic pancreatitis was not differentially influenced by either analgesic. In conclusion, both analgesics can be used during 33 days of chronic pancreatitis, but tramadol seems to be moderately advantageous when compared to metamizole.

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

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.

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