scholarly journals Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders

2020 ◽  
Vol 54 (6) ◽  
pp. 1199-1217
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Sequencing Analysis ◽  
Obesogenic Diet

Background/Aims: Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females. Methods: Wild type (WT) and miRNA-22 knockout (miRNA-22 KO) females were fed a control or an obesogenic diet. Body weight gain, adiposity, glucose tolerance, insulin tolerance, and plasma levels of total cholesterol and triglycerides were measured. Cardiac and white adipose tissue remodeling was assessed by histological analyses. Echocardiography was used to evaluate cardiac function and morphology. RNA-sequencing analysis was employed to characterize mRNA expression profiles in female hearts. Results: Loss of miRNA-22 attenuated body weight gain, adiposity, and prevented obesogenic diet-induced insulin resistance and dyslipidemia in females. WT obese females developed cardiac hypertrophy. Interestingly, miRNA-22 KO females displayed cardiac hypertrophy without left ventricular dysfunction and myocardial fibrosis. Both miRNA-22 deletion and obesogenic diet changed mRNA expression profiles in female hearts. Enrichment analysis revealed that genes associated with regulation of the force of heart contraction, protein folding and fatty acid oxidation were enriched in hearts of WT obese females. In addition, genes related to thyroid hormone responses, heart growth and PI3K signaling were enriched in hearts of miRNA-22 KO females. Interestingly, miRNA-22 KO obese females exhibited reduced mRNA levels of Yap1, Egfr and Tgfbr1 compared to their respective controls. Conclusion: This study reveals that miRNA-22 deletion induces cardiac hypertrophy in females without affecting myocardial function. In addition, our findings suggest miRNA-22 as a potential therapeutic target to treat obesity-related metabolic disorders in females.

scholarly journals Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity

2019 ◽  
Author(s):  
Lidewij Schipper ◽  
Steffen van Heijningen ◽  
Giorgio Karapetsas ◽  
Eline M. van der Beek ◽  
Gertjan van Dijk
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Energy Intake ◽  
White Adipose Tissue ◽  
Body Weight Gain ◽  
Tissue Mass ◽  
Individual Housing ◽  
Adipose Tissue Mass ◽  
Obesogenic Diet

AbstractIndividual housing from weaning onwards resulted in reduced growth rate during adolescence in male C57Bl/6J mice that were housed individually, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice. Body weight gain of individually housed animals exceeded that of socially housed mice during adulthood, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition. This study shows that post-weaning individual housing of male mice results in impaired adolescent growth and higher susceptibility to obesity in adulthood. Mice are widely used to study obesity and cardiometabolic comorbidities. For (metabolic) research models using mice, (social) housing practices should be carefully considered and regarded as a potential confounder due to their modulating effect on metabolic health outcomes.

Comparative effects of tamoxifen and angiotensin II type-1 receptor antagonist therapy on the hemodynamic profile of the ovariectomized female rat

2003 ◽  
Vol 81 (9) ◽  
pp. 915-919 ◽  
Author(s):  
My-Lan Pham-Dang ◽  
Robert Clement ◽  
Isabelle Mercier ◽  
Angelino Calderone
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Body Weight Gain ◽  
Left Ventricular ◽  
Female Rat ◽  
Ovx Rats ◽  
Hemodynamic Profile

Hormonal replacement therapy (HRT) has failed to provide a cardioprotective action in postmenopausal women, and thus alternative pharmacological approaches are required. The present study examined the therapeutic potential of the partial estrogen receptor agonist tamoxifen and the angiotensin II type-1 receptor antagonist irbesartan on the hemodynamic profile of ovariectomized (OVX) female Sprague–Dawley rats (9–11 weeks). Three weeks following ovariectomy, uterine atrophy was evident and body weight was increased as compared with sham-operated animals. Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and mean arterial pressure (MAP) were significantly increased in the OVX rats as compared with sham rats. One week following ovariectomy, rats were treated with either tamoxifen (10 mg kg–1 day–1) or irbesartan (40 mg kg–1 day–1) for a period of 2 weeks. The administration of tamoxifen to OVX rats partially reversed uterine atrophy and prevented body weight gain, albeit body weight remained significantly lower than in sham-operated animals. LVSP and LVEDP were normalized in the tamoxifen-treated OVX rats, whereas MAP remained elevated. Irbesartan partially reduced the body weight gain of the OVX rats and did not influence uterine atrophy. LVSP and MAP were normalized in irbesartan-treated OVX rats, whereas LVEDP remained elevated. These data demonstrate that irbesartan rather than tamoxifen was efficacious in normalizing MAP in the OVX rats without a secondary effect on the uterus.Key words: ovariectomy, hemodynamics, tamoxifen, AT1 receptor antagonists.

scholarly journals Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle

2020 ◽  
Vol 134 (13) ◽  
pp. 1659-1673
Author(s):  
Anwar Khan ◽  
Sherouk Fouda ◽  
Ali Mahzari ◽  
Stanley M.H. Chan ◽  
Xiu Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cigarette Smoking ◽  
Mrna Expression ◽  
Glucose Intolerance ◽  
Insulin Action ◽  
Insulin Signalling ◽  
Body Weight Gain ◽  
Hormone Sensitive Lipase ◽  
Reduced Body

Abstract Cigarette smoking (CS) is known to reduce body weight and this often masks its real effect on insulin action. The present study tested the hypothesis that CS can divert lipid deposition to muscles to offset the supposed benefit of reduced body weight gain on insulin signalling in this major site for glucose tolerance (or insulin action). The study was conducted in mice exposed to chronic CS followed by either a chow (CH) diet or a high-fat (HF) diet. CS increased triglyceride (TG) levels in both plasma and muscle despite a reduced body weight gain and adiposity. CS led to glucose intolerance in CH-fed mice and they retained the glucose intolerance that was induced by the HF diet. In adipose tissue, CS increased macrophage infiltration and the mRNA expression of TNFα but suppressed the protein expression of adipose triglyceride lipase and PPARγ. While CS increased hormone-sensitive lipase and suppressed the mRNA expression of leptin, these effects were blunted in HF-fed mice. These results imply that CS impairs insulin signalling in skeletal muscle via accumulated intramuscular lipids from lipolysis and lipodystrophy of adipose tissues. This may explain why smokers may not benefit from insulin sensitising effects of reduced body weight gain.

scholarly journals Gut microbiota in obesity and metabolic disorders

2010 ◽  
Vol 69 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Yolanda Sanz ◽  
Arlette Santacruz ◽  
Paola Gauffin
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Dietary Intervention ◽  
Body Weight Gain ◽  
Human Subjects ◽  
Inflammatory Factors ◽  
Public Health Issue ◽  
Immune Functions

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

scholarly journals Ginger Water Reduces Body Weight Gain and Improves Energy Expenditure in Rats

Foods ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 38 ◽  
Author(s):  
Samy Sayed ◽  
Mohamed Ahmed ◽  
Ahmed El-Shehawi ◽  
Mohamed Alkafafy ◽  
Saqer Al-Otaibi ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Mrna Expression ◽  
Glucose Transporter ◽  
Body Weight Gain ◽  
Regulatory Element ◽  
Transcriptional Level ◽  
Tissue Samples ◽  
Glucose Transporter 2

Obesity is a serious global problem that causes predisposition to numerous serious diseases. The current study aims to investigate the effect of ginger water on body weight and energy expenditure through modulation of mRNA expression of carbohydrate and lipid metabolism. A white colored liquid obtained during freeze-drying of fresh rhizomes of Zingiber officinal was collected and named ginger water. It was used to treat rats, then blood and tissue samples were collected from the liver and white adipose at the end of the experiment. The serum was prepared and used for biochemical assays, while tissue samples were used for RNA isolation and gene expression analysis via Reverse transcription polymerase chain reaction (RT-PCR). Results of High Performance Liquid Chromatography (HPLC) analysis of ginger water revealed the presence of chrysin and galangin at concentrations of 0.24 µg/mL and 0.53 µg/mL, respectively. Average body weight gain decreased significantly in groups that received ginger water. In addition, both total cholesterol and serum triacylglycerol were reduced in the groups that received ginger water. Furthermore, mRNA expression of Sterol regulatory element-binding protein 1 (SREBP-1c) in the liver and leptin in adipose tissues were downregulated, while those of adiponectin, hepatic carnitine palmitoyltransferase1 (CPT-1), acyl-coA oxidase (ACO), Glucose transporter 2 (GLUT-2), and pyruvate kinase (PK) were upregulated in ginger water-treated groups. These results clearly revealed the lowering body weight gain effect of ginger water, which most likely occurs at the transcriptional level of energy metabolizing proteins.

scholarly journals Insights into the Roles of Gut Microbes in Obesity

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Yolanda Sanz ◽  
Arlette Santacruz ◽  
Giada De Palma
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Cholesterol Metabolism ◽  
Body Weight Gain ◽  
Inflammatory Factors ◽  
Public Health Issue ◽  
Low Grade ◽  
Gut Microbes

Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the host's ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders.

scholarly journals Effects of IGF-I on cardiac growth and expression of mRNAs coding for cardiac proteins after induction of heart hypertrophy in the rat

1998 ◽  
pp. 109-117 ◽  
Author(s):  
MY Donath ◽  
W Zierhut ◽  
MA Gosteli-Peter ◽  
C Hauri ◽  
ER Froesch ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Left Ventricle ◽  
Body Weight Gain ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Heart Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Igf I ◽  
Alpha Actin

Adult rat cardiomyocytes in long-term culture reexpress several fetal cardiac proteins which also reappear during overload heart hypertrophy in vivo. IGF-I decreases reexpression of some of these proteins and stimulates myofibrillogenesis. IGF-I might therefore contribute to enhancing readaptation of the heart to overload. In order to test this hypothesis, hypertension was induced in male Wistar Kyoto rats by constriction of the left renal artery, and an infusion of 500 microg/day of recombinant human IGF-I (rhIGF-I) or vehicle was started after the operation via intraabdominally implanted osmotic minipumps. In the vehicle-treated hypertensive animals body weight gain was reduced after 3, 7 and 14 days, whereas rhIGF-I-treated hypertensive animals continued to gain weight like sham-operated animals. Left ventricular weight and the left, but not the right ventricle/body weight ratio increased more in rhIGF-I- than in vehicle-infused rats. Left ventricular IGF-I mRNA levels remained unchanged after renal clipping in both vehicle- and rhIGF-I-treated rats. However, beta-myosin heavy chain (MHC) mRNA in the left ventricle was 6- to 10-fold increased in clipped controls during the whole postoperative period, and rhIGF-I reduced this increase by more than 50% on days 7 and 14. On the first postoperative day, rhIGF-I prevented the decrease (50%) of alpha-MHC mRNA and the increase (2.5-fold of atrial natriuretic factor mRNA in the left ventricle. Renal clipping did not alter cardiac alpha-actin, but enhanced skeletal alpha-actin mRNA expression in the left ventricle up to 2.5-fold. However, both mRNAs were unaffected by rhIGF-I treatment. Restoration of body weight gain and stimulation of left ventricular cardiac weight by rhIGF-I as well as partial reversion of hypertension-induced changes in cardiac protein expression may reflect beneficial effects contributing to enhance readaptation of the heart to overload.

scholarly journals RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance

2021 ◽  
Vol 14 (11) ◽  
pp. 1178
Author(s):  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Er Stress ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Normal Diet ◽  
High Fat

Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.

scholarly journals Microglia–Neuron Crosstalk in Obesity: Melodious Interaction or Kiss of Death?

2021 ◽  
Vol 22 (10) ◽  
pp. 5243
Author(s):  
Stéphane Léon ◽  
Agnès Nadjar ◽  
Carmelo Quarta
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Neuronal Circuits ◽  
Mechanistic Studies ◽  
The Core ◽  
Diet Induced Obesity ◽  
The Brain

Diet-induced obesity can originate from the dysregulated activity of hypothalamic neuronal circuits, which are critical for the regulation of body weight and food intake. The exact mechanisms underlying such neuronal defects are not yet fully understood, but a maladaptive cross-talk between neurons and surrounding microglial is likely to be a contributing factor. Functional and anatomical connections between microglia and hypothalamic neuronal cells are at the core of how the brain orchestrates changes in the body’s metabolic needs. However, such a melodious interaction may become maladaptive in response to prolonged diet-induced metabolic stress, thereby causing overfeeding, body weight gain, and systemic metabolic perturbations. From this perspective, we critically discuss emerging molecular and cellular underpinnings of microglia–neuron communication in the hypothalamic neuronal circuits implicated in energy balance regulation. We explore whether changes in this intercellular dialogue induced by metabolic stress may serve as a protective neuronal mechanism or contribute to disease establishment and progression. Our analysis provides a framework for future mechanistic studies that will facilitate progress into both the etiology and treatments of metabolic disorders.

Sign in / Sign up

Export Citation Format

Share Document