Dnmt2-null sperm block maternal transmission of a paramutant phenotype

2021 ◽  
Author(s):  
Tian Yu ◽  
Yeming Xie ◽  
Chong Tang ◽  
Yue Wang ◽  
Shuiqiao Yuan ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Small Rnas ◽  
Metabolic Disorders ◽  
Wild Type ◽  
Maternal Transmission ◽  
High Fat ◽  
Small Noncoding Rnas ◽  
Male Germline ◽  
Tail Tip ◽  
Female Germline

Abstract Previous studies have shown that Dnmt2-null sperm block the paternal transmission (through sperm) of certain acquired traits, e.g., high fat diet-induced metabolic disorders or white tails due to a Kit paramutation. Here, we report that DNMT2 is also required for the transmission of a Kit paramutant phenotype (white tail tip) through the female germline (i.e., oocytes). Specifically, ablation of Dnmt2 led to aberrant profiles of tRNA-derived small RNAs (tsRNAs) and other small noncoding RNAs (sncRNAs) in sperm, which correlate with altered mRNA transcriptomes in pronuclear zygotes derived from wild type oocytes carrying the Kit paramutation and a complete blockage of transmission of the paramutant phenotype through oocytes. Together, the present study suggests that both paternal and maternal transmission of epigenetic phenotypes requires intact DNMT2 functions in the male germline.

Abstract P312: The Essential Role Of Prak In Preserving Cardiac Function And Insulin Resistance In High Fat Diet-induced Diabetes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Yu T Zhao ◽  
Jianfeng Du ◽  
Thomas J Zhao ◽  
Hao Wang ◽  
Marshall Kadin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Function ◽  
Western Blot ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Tolerance Test ◽  
Wild Type ◽  
High Fat

Background: p38 regulated/activated protein kinase (PRAK) plays a crucial role in modulating cell death and survival. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high fat diet (HFD). Methods: Wild type and PRAK -/- mice at 8 weeks old were exposed to either chow food or HFD for a consecutive 16 weeks. Glucose tolerance test and insulin tolerance test were employed to assess insulin resistance. Echocardiography was employed to assess myocardial function. Western blot was used to determine the molecular signaling involved in phosphorylation of IRS-1, AMPKα, ERK-44/42, and irisin. Real time-PCR was used to assess the hypertrophic genes of the myocardium. Histological analysis was employed to assess the hypertrophic response, interstitial myocardial fibrosis, and apoptosis in the heart. Results: HFD induced metabolic stress is indicated by glucose intolerance and insulin intolerance. PRAK knockout aggravated insulin resistance, as indicated by glucose intolerance and insulin intolerance testing as compared to wild type littermates. As compared to wild type, hyperglycemia and hypercholesterolemia were manifested in PRAK-knockout mice following high fat diet intervention. High fat diet intervention displayed a decline in fractional shortening (FS) and ejection fraction (EF). However, deletion of PRAK exacerbated the decline in EF and FS as compared to wild type mice following HFD treatment. In addition, PRAK knockout mice enhanced the expression of myocardial hypertrophic genes including ANP, BNP, and βMHC in HFD treatment, which was also associated with an increase in cardiomyocyte size and interstitial fibrosis. Western blot indicated that deletion of PRAK induces decreases in phosphorylation of IRS-1, AMPKα, and ERK44/42 as compared to wild type controls. Conclusion: Our finding indicates that deletion of PRAK promoted myocardial dysfunction, cardiac remodeling, and metabolic disorders in response to HFD.

scholarly journals The Essential Role of PRAK in Preserving Cardiac Function and Insulin Resistance in High-Fat Diet-Induced Diabetes

2021 ◽  
Vol 22 (15) ◽  
pp. 7995
Author(s):  
Jianfeng Du ◽  
Yu Tina Zhao ◽  
Hao Wang ◽  
Ling X. Zhang ◽  
Gangjian Qin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Function ◽  
Western Blot ◽  
Glucose Intolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Wild Type ◽  
High Fat

Regulated/activated protein kinase (PRAK) plays a crucial role in modulating biological function. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high-fat diet (HFD). Wild-type and PRAK−/− mice at 8 weeks old were exposed to either chow food or HFD for a consecutive 16 weeks. Glucose tolerance tests and insulin tolerance tests were employed to assess insulin resistance. Echocardiography was employed to assess myocardial function. Western blot was used to determine the molecular signaling involved in phosphorylation of IRS-1, AMPKα, ERK-44/42, and irisin. Real time-PCR was used to assess the hypertrophic genes of the myocardium. Histological analysis was employed to assess the hypertrophic response, interstitial myocardial fibrosis, and apoptosis in the heart. Western blot was employed to determine cellular signaling pathway. HFD-induced metabolic stress is indicated by glucose intolerance and insulin intolerance. PRAK knockout aggravated insulin resistance, as indicated by glucose intolerance and insulin intolerance testing as compared with wild-type littermates. As compared with wild-type mice, hyperglycemia and hypercholesterolemia were manifested in PRAK-knockout mice following high-fat diet intervention. High-fat diet intervention displayed a decline in fractional shortening and ejection fraction. However, deletion of PRAK exacerbated the decline in cardiac function as compared with wild-type mice following HFD treatment. In addition, PRAK knockout mice enhanced the expression of myocardial hypertrophic genes including ANP, BNP, and βMHC in HFD treatment, which was also associated with an increase in cardiomyocyte size and interstitial fibrosis. Western blot indicated that deletion of PRAK induces decreases in phosphorylation of IRS-1, AMPKα, and ERK44/42 as compared with wild-type controls. Our finding indicates that deletion of PRAK promoted myocardial dysfunction, cardiac remodeling, and metabolic disorders in response to HFD.

2038-P: Rice Endosperm Protein Intake in Childhood Suppresses the Development of High-Fat Diet-Induced Metabolic Disorders and Kidney Disease during Adulthood in Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2038-P
Author(s):  
YUKI HIGUCHI ◽  
MICHIHIRO HOSOJIMA ◽  
HIDEYUKI KABASAWA ◽  
SHOJI KUWAHARA ◽  
RYOHEI KASEDA ◽  
...  
Keyword(s):  
Kidney Disease ◽  
High Fat Diet ◽  
Protein Intake ◽  
Metabolic Disorders ◽  
High Fat ◽  
Rice Endosperm ◽  
Endosperm Protein

The beneficial effects of Lactobacillus fermented black barley on high fat diet-induced fatty liver in rats

2021 ◽  
Author(s):  
Qi Guan ◽  
Xinwen Ding ◽  
Lingyue Zhong ◽  
Chuang Zhu ◽  
Pan Nie ◽  
...  
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
High Fat ◽  
Beneficial Effects ◽  
Phytochemical Composition

Long term high-fat diet (HF) can cause metabolic disorders, which might induce fatty liver. Fermented whole cereal food exhibit healthy potential due to their unique phytochemical composition and probiotics. In...

DHA-enriched phospholipids from large yellow croaker roe regulate lipid metabolic disorders and gut microbiota imbalance on SD rats with a high-fat diet

2021 ◽  
Author(s):  
Xiaodan Lu ◽  
Rongbin Zhong ◽  
Ling Hu ◽  
Luyao Huang ◽  
Lijiao Chen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Gut Microbiota ◽  
Polyunsaturated Fatty Acids ◽  
High Fat Diet ◽  
Nutritional Value ◽  
Metabolic Disorders ◽  
Large Yellow Croaker ◽  
High Fat ◽  
Sd Rats

Abstract Large yellow croaker roe phospholipids (LYCRPLs) has great nutritional value because of containing rich docosahexaenoic acid (DHA), which is a kind of n-3 polyunsaturated fatty acids (n-3 PUFAs). In...

scholarly journals Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Receptor Expression ◽  
Wild Type ◽  
High Fat ◽  
Renal Gluconeogenesis ◽  
Mrna And Protein Expression ◽  
Polymerase Chain ◽  
Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice

2016 ◽  
Vol 50 (3) ◽  
pp. 314-327 ◽  
Author(s):  
Bin Feng ◽  
Ran Meng ◽  
Bin Huang ◽  
Shanmei Shen ◽  
Yan Bi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
High Fat ◽  
Hepatic Oxidative Stress

scholarly journals 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

2012 ◽  
Vol 302 (6) ◽  
pp. E654-E665 ◽  
Author(s):  
Banumathi K. Cole ◽  
Norine S. Kuhn ◽  
Shamina M. Green-Mitchell ◽  
Kendall A. Leone ◽  
Rebekah M. Raab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Stress Markers ◽  
Deficient Mice

Central obesity is associated with chronic inflammation, insulin resistance, β-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

Sign in / Sign up

Export Citation Format

Share Document