High fat diet feeding results in gender specific steatohepatitis and inflammasome activation

AbstractNLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

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The regulation of hepatic Pon1 by a maternal high-fat diet is gender specific and may occur through promoter histone modifications in neonatal rats

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2013.09.016 ◽

2014 ◽

Vol 25 (2) ◽

pp. 170-176 ◽

Cited By ~ 23

Author(s):

Rita S. Strakovsky ◽

Xiyuan Zhang ◽

Dan Zhou ◽

Yuan-Xiang Pan

Keyword(s):

Histone Modifications ◽

High Fat Diet ◽

Neonatal Rats ◽

High Fat ◽

Gender Specific

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Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release

Journal of Immunology Research ◽

10.1155/2018/2481418 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Shengnan Zhao ◽

Zizhen Gong ◽

Xixi Du ◽

Chunyan Tian ◽

Lingyu Wang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

High Fat Diet ◽

Cathepsin B ◽

Intestinal Inflammation ◽

Critical Role ◽

Inflammasome Activation ◽

High Fat ◽

Molecular Pattern ◽

Nlrp3 Inflammasome Activation ◽

Sphingosine 1 Phosphate

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

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Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender

International Journal of Molecular Sciences ◽

10.3390/ijms19123948 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3948 ◽

Cited By ~ 15

Author(s):

Cristiana Porcu ◽

Silvia Sideri ◽

Maurizio Martini ◽

Alessandra Cocomazzi ◽

Andrea Galli ◽

...

Keyword(s):

High Fat Diet ◽

Liver Steatosis ◽

Normal Diet ◽

Male Mice ◽

High Fat ◽

Unhealthy Diet ◽

Autophagic Process ◽

Related Proteins ◽

Gender Specific ◽

Novel Therapeutic

Oleuropein (Ole) is one of the most plentiful phenolic compounds with antioxidant, anti-inflammatory, anti-atherogenic, hypoglycemic and hypolipidemic effects. The aim of our study was to establish whether the positive Ole-related effects on liver steatosis could be associated with autophagy. Female and male C57BL/6J mice were fed normal diet (ND) or high-fat diet (HFD) for eight weeks, and Ole was added or not for the following eight weeks. The autophagy-related proteins Akt, mTOR, AMPK, ULK1, Beclin-1, LC3B and p62/Sqstm1 were analyzed. Interestingly, Ole induced a different regulation of the Akt/mTOR pathway in female compared to male mice, but was able to activate the autophagic process in ND and HFD mice through AMPK-dependent phosphorylation of ULK1 at Ser555, regardless of the gender. Our work reveals the ability of Ole to induce, in liver of ND and HFD mice, autophagy independently by gender-specific mTOR activation. We highlight Ole as a novel therapeutic approach to counteract unhealthy diet-related liver steatosis by targeting autophagy.

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Psychosocial, Eating Behavior, and Lifestyle Factors Influencing Overweight and Obesity in Adolescents

Food and Nutrition Bulletin ◽

10.1177/0379572121992750 ◽

2021 ◽

Vol 42 (1_suppl) ◽

pp. S72-S91

Author(s):

Rina Agustina ◽

Meilianawati ◽

Fenny ◽

Atmarita ◽

Suparmi ◽

...

Keyword(s):

Depressive Symptoms ◽

High Fat Diet ◽

Public Health Problem ◽

School Enrollment ◽

Overweight And Obesity ◽

High Fat ◽

Older Adolescents ◽

Adolescent Overweight ◽

Lower Education ◽

Gender Specific

Background: Adolescent overweight and obesity (AOO) is a global public health problem and risk for noncommunicable diseases. Understanding context-specific risks is crucial for interventions. Objective: Determine the prevalence of AOO in the Indonesian National Health Survey (INHS) 2013, assess the 5-year trend from 2013 to 2018, and identify risks. Methods: We selected adolescents aged 10 to 19 years (n = 174 290) from the INHS 2013 and used hierarchical logistic regression to identify gender-specific risks for those aged 15 to 19 years (n = 77 534). Change in AOO was assessed by comparison to INHS 2018 reports. Results: The national AOO prevalence increased over 5 years by 48% in young adolescents (13-15 years) and 85% in older ones (16-18 years). High prevalence areas included the urban location of Jakarta (20.9%) and the remote rural region of Papua (19.4%). Overall, AOO risks were being sedentary, male, lower education, married, younger adolescent, and school enrollment, with urban residence and higher wealth being persistent risks for all analyses. Data for depressive symptoms were available for older adolescents whose additional risks were being sedentary, depressive symptoms, and high-fat diet. Male risks were being sedentary and lower education, and female risks were being married, depressive symptoms, high-fat intake, and lower education. Higher intake of fruits and vegetables and fewer sweets did not protect against AOO if a high-fat diet was consumed. Conclusions: Adolescent overweight and obesity in Indonesia is rapidly increasing, especially in older adolescents and males, and with gender-specific risks. Customized multisectoral interventions to identify strategies for lifestyle change are urgently needed.

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