scholarly journals Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription

2008 ◽  
Vol 295 (3) ◽  
pp. H1206-H1215 ◽  
Author(s):  
Cindy X. Fang ◽  
Feng Dong ◽  
D. Paul Thomas ◽  
Heng Ma ◽  
Leilei He ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Palmitic Acid ◽  
High Fat Diet ◽  
Weight Control ◽  
Dominant Negative ◽  
High Fat ◽  
Forkhead Transcription Factor ◽  
Diet Induced Obesity ◽  
Intracellular Ca

Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed to evaluate the role of Akt, the forkhead transcription factor Foxo3a, and atrophy genes muscle-specific RING finger (MuRF)-1 and atrogin-1 in cardiac hypertrophy and contractile dysfunction associated with high-fat diet-induced obesity. Mice were fed a low- or high-fat diet for 6 mo along with a food-restricted high-fat weight control group. Echocardiography revealed decreased fractional shortening and increased end-systolic diameter and cardiac hypertrophy in high-fat obese but not in weight control mice. Cardiomyocytes from high-fat obese but not from weight control mice displayed contractile and intracellular Ca2+ defects including depressed maximal velocity of shortening/relengthening, prolonged duration of shortening/relengthening, and reduced intracellular Ca2+ rise and clearance. Caspase activities were greater in high-fat obese but not in weight control mouse hearts. Western blot analysis revealed enhanced basal Akt and Foxo3a phosphorylation and reduced insulin-stimulated phosphorylation of Akt and Foxo3a without changes in total protein expression of Akt and Foxo3a in high-fat obese hearts. RT-PCR and immunoblotting results displayed reduced levels of the atrogens atrogin-1 and MuRF-1, the upregulated hypertrophic markers GATA4 and ciliary neurotrophic factor receptor-α, as well as the unchanged calcineurin and proteasome ubiquitin in high-fat obese mouse hearts. Transfection of H9C2 myoblast cells with dominant-negative Foxo3a adenovirus mimicked palmitic acid (0.8 mM for 24 h)-induced GATA4 upregulation without an additive effect. Dominant-negative Foxo3a-induced upregulation of pAkt and repression of phosphatase and tensin homologue were abrogated by palmitic acid. These results suggest a cardiac hypertrophic response in high-fat diet-associated obesity at least in part through inactivation of Foxo3a by the Akt pathway.

scholarly journals The “metabolic sensor” function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity

2016 ◽  
Vol 310 (4) ◽  
pp. R337-R345 ◽  
Author(s):  
Celia D. Sladek ◽  
Wanida Stevens ◽  
Zhilin Song ◽  
Ginger C. Johnson ◽  
Paul S. MacLean
Keyword(s):  
High Fat Diet ◽  
Supraoptic Nucleus ◽  
Insulin Receptors ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Intracellular Ca ◽  
Metabolic Sensor ◽  
Vasopressin Neurons ◽  
Established Role

The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of “metabolic sensors”. They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca2+] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity.

High-fat diet leads to elevated lipid accumulation and endoplasmic reticulum stress in oocytes, causing poor embryo development

2020 ◽  
Vol 32 (14) ◽  
pp. 1169
Author(s):  
Arpitha Rao ◽  
Aparna Satheesh ◽  
Guruprasad Nayak ◽  
Pooja Suresh Poojary ◽  
Sandhya Kumari ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Developmental Potential ◽  
Diet Induced Obesity ◽  
Activating Transcription Factor ◽  
Elevated Lipid

The present study was designed to investigate the effect of diet-induced obesity on endoplasmic reticulum (ER) stress in oocytes. Swiss albino mice (3 weeks old) were fed with a high-fat diet (HFD) for 8 weeks. Oocytes were assessed for lipid droplet accumulation, oxidative stress, ER stress and their developmental potential invitro. High lipid accumulation (P<0.01) and elevated intracellular levels of reactive oxygen species were observed in both germinal vesicle and MII oocytes of HFD-fed mice (P<0.05 and P<0.01 respectively compared with control). Further, expression of the ER stress markers X-box binding protein 1 (XBP1), glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4) and activating transcription factor 6 (ATF6) was significantly (P<0.001) higher in oocytes of the HFD than control group. Oocytes from HFD-fed mice exhibited poor fertilisation and blastocyst rates, a decrease in total cell number and high levels of DNA damage (P<0.01) compared with controls. In conclusion, diet-induced obesity resulted in elevated lipid levels and higher oxidative and ER stress in oocytes, which contributed to the compromised developmental potential of embryos.

Ameliorative effect of selegiline in high fat diet induced obesity rat model: Possible role of dopaminergic pathway

2020 ◽  
Vol 20 ◽  
pp. 100301
Author(s):  
Amit Goyal ◽  
Ankita Sharma ◽  
Deepika Sharma ◽  
Tapan Behl ◽  
Anjoo Kamboj ◽  
...  
Keyword(s):  
Rat Model ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Dopaminergic Pathway ◽  
Ameliorative Effect

scholarly journals Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice

2014 ◽  
Vol 89 (3) ◽  
pp. 399-412 ◽  
Author(s):  
Krisstonia Spruiell ◽  
Dominique Z. Jones ◽  
John M. Cullen ◽  
Emmanuel M. Awumey ◽  
Frank J. Gonzalez ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Pregnane X Receptor ◽  
High Fat ◽  
Female Mice ◽  
Diet Induced Obesity

scholarly journals Potential Role of Central Microglia Activation in High Fat Diet‐Induced Obesity

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Aneesh Singal ◽  
Caitlin R. Coker ◽  
Sarah S. Bingaman ◽  
Amy C. Arnold ◽  
Yuval Silberman
Keyword(s):  
High Fat Diet ◽  
Potential Role ◽  
Microglia Activation ◽  
High Fat ◽  
Diet Induced Obesity

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

2020 ◽  
Vol 34 (3) ◽  
Author(s):  
Rasha Abdelmawla Ghazala ◽  
Azza El Medney ◽  
Anisa Meleis ◽  
Passant Mohie El dien ◽  
Hend Samir
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Anti Inflammatory

scholarly journals Colonic dysmotility and inflammation associated with high fat diet-induced obesity: role of the enteric glia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Matteo Fornai ◽  
Carolina Pellegrini ◽  
Vanessa D'Antongiovanni ◽  
Laura Benvenuti ◽  
Nunzia Bernardini ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Mucosal Barrier ◽  
Tlr4 Expression ◽  
High Fat ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Epididymal Fat ◽  
Junction Protein ◽  
Colonic Dysmotility

AbstractIntroductionEnteric glial cells (EGCs) contribute to the regulation of bowel motility, and have been implicated in the onset and development of several digestive disorders. However, the involvement of EGCs in obesity-related intestinal dysmotility is unknown. Accordingly, this study examined the role of EGCs in colonic neuromuscular dysfunctions in a mouse model of diet-induced obesity.Materials and MethodsC57BL/6 male mice (n = 6 per group) were fed with standard diet (SD) or high fat diet (HFD) for 8 weeks. Body and epididymal fat weight, and blood fasting glucose levels were evaluated the day before sacrifice. Colonic longitudinal muscle strips were set up in organ baths with Krebs solution and connected to isometric transducers. The effects of fluorocitrate (FC, gliotoxin) were tested on contractile responses mediated by NK1 tachykininergic receptors upon application of electrical stimuli (0.5 ms, 28 V, 10 Hz) [incubation with atropine, guanethidine, L-NAME, GR159897 and SB218795 (NK2 and NK3 antagonists, respectively)] or exogenous substance P (SP). Colonic levels of interleukin (IL)-1β, IL-6, malondialdehyde (MDA) and occludin (a tight junction protein involved the maintenance of mucosal barrier) were measured. Cultured rat EGCs were exposed to palmitate and lipopolysaccharide (LPS), either alone or in combination, to mimic the exposure to HFD. IL-1β and SP levels were then assessed in cell supernatants, while toll-like receptor 4 (TLR4) expression was evaluated in cell lysates.ResultsHFD-mice displayed increments of body weight, epididymal fat weight and blood glucose levels. In in vitro experiments, electrically induced colonic tachykininergic contractions were enhanced in HFD mice, as compared with SD animals. No differences were observed when comparing contractions to exogenous SP. The increase in electrically evoked tachykininergic contractions was blunted upon incubation with the gliotoxin FC. Exogenous SP-induced contractions were not affected by FC. HFD mice displayed an increase in colonic IL-1β, IL-6 and MDA levels and a reduced occludin expression, as compared with SD mice. Exposure of EGCs to palmitate, alone or in combination with LPS, resulted in a significant increase in TLR4 expression, while LPS alone was without effects. The combination of palmitate and LPS increased significantly IL-1β and SP levels in cell supernatants, while single treatments were without effects.DiscussionHFD is characterized by colonic dysmotility along with bowel inflammation, oxidative stress, and an impairment of mucosal barrier integrity. In this setting, the hyperactivation of EGCs, likely via TLR4, appears to contribute to inflammation and colonic tachykininergic motor dysfunctions.

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