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

2018 ◽  
Vol 19 (12) ◽  
pp. 3948 ◽  
Author(s):  
Cristiana Porcu ◽  
Silvia Sideri ◽  
Maurizio Martini ◽  
Alessandra Cocomazzi ◽  
Andrea Galli ◽  
...  

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.

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3187
Author(s):  
Eunkuk Park ◽  
Chang-Gun Lee ◽  
Hyoju Jeon ◽  
Hyesoo Jeong ◽  
Subin Yeo ◽  
...  

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.


Endocrinology ◽  
2021 ◽  
Author(s):  
Silas A Culver ◽  
Safia Akhtar ◽  
Callie Rountree-Jablin ◽  
Susanna R Keller ◽  
Helen P Cathro ◽  
...  

Abstract ATP6AP2 expression is increased in the nephron during high fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week old male C57BL/6J mice with inducible nephron specific ATP6AP2 KO and non-induced controls (C) were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (p<0.01) lower WT compared to C. HFD fed mice had 41% (p<0.05) greater WT than ND fed C. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (p<0.05). Mice on HFD had less caloric intake compared to ND controls (p<0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.


Author(s):  
Collins NIMAKO ◽  
Yoshinori IKENAKA ◽  
Yuko OKAMATSU-OGURA ◽  
Jussiaea V. BARIUAN ◽  
Atsushi KOBAYASHI ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1148
Author(s):  
Maria Kaare ◽  
Kaie Mikheim ◽  
Kersti Lilleväli ◽  
Kalle Kilk ◽  
Toomas Jagomäe ◽  
...  

In the large GWAS studies, NEGR1 gene has been one of the most significant gene loci for body mass phenotype. The purpose of the current study was to clarify the role of NEGR1 in the maintenance of systemic metabolism, including glucose homeostasis, by using both male and female Negr1−/− mice receiving a standard or high fat diet (HFD). We found that 6 weeks of HFD leads to higher levels of blood glucose in Negr1−/− mice. In the glucose tolerance test, HFD induced phenotype difference only in male mice; Negr1−/− male mice displayed altered glucose tolerance, accompanied with upregulation of circulatory branched-chain amino acids (BCAA). The general metabolomic profile indicates that Negr1−/− mice are biased towards glyconeogenesis, fatty acid synthesis, and higher protein catabolism, all of which are amplified by HFD. Negr1 deficiency appears to induce alterations in the efficiency of energy storage; reduced food intake could be an attempt to compensate for the metabolic challenge present in the Negr1−/− males, particularly during the HFD exposure. Our results suggest that the presence of functional Negr1 allows male mice to consume more HFD and prevents the development of glucose intolerance, liver steatosis, and excessive weight gain.


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Saoraya Chanmuang ◽  
Orawan Meemalai ◽  
Kitipong Promyo ◽  
Kyung-Hee Park ◽  
Suthipong Pongworn ◽  
...  

Abstract Endothelial dysfunction is directly involved in consequence of various metabolic syndromes such as diabetes and hypertension. In this study, we investigated the preventive effects of two ark clams [ark shell (AS, Scapharca subcrenata) and granular ark (GA, Tegillarca granosa)] on endothelial dysfunction induced by a high-fat diet. Wistar rats were divided into four groups as follows: control (normal diet), HF (high-fat diet), AS (high-fat diet + 5% AS powder), and GA (high-fat diet + 5% GA powder) for 12 weeks. AS and GA diets enhanced vascular reactivity of the rat thoracic aorta and significantly increased expression levels of vascular relaxation-related proteins (p-Akt-ser473 and p-eNOS-ser1177). Ark clam supplement reduced endothelin-1 expression level, as compared to the HF group. Additionally, AS and GA showed a trend of improving insulin sensitivity compared to HF. Our results suggest that AS and GA enhance vascular reactivity and ameliorated endothelial dysfunction induced by a high-fat diet.


2017 ◽  
Vol 33 (1) ◽  
pp. 177-190 ◽  
Author(s):  
Huali Wu ◽  
Qiongzhen Liu ◽  
Praveen Kumar Kalavagunta ◽  
Qiaoling Huang ◽  
Wenting Lv ◽  
...  

2021 ◽  
Vol 20 (3) ◽  
pp. 280-289
Author(s):  
Parisa Norouzzadeh ◽  
◽  
Roghayeh Pouzesh Jadidi ◽  

Background and Objectives: This study aimed to determine the effect of a course of aerobic exercise with a high-fat diet on eNOS and ROS in testicular tissue of adolescent male rats. Subjects and Methods A total of 40 adolescent male rats (30 days old) were randomized in the following groups: normal diet control, normal diet training, high fat diet control, and high-fat diet training. The high-fat diet rats were under a high-fat regimen (5.817 kcal/g) for 30 days, and then a normal fat diet (3.801 kcal/g) was continued after the 60th day of birth. Aerobic training was conducted for four weeks included three training sessions from the 70th to 98th days of life. Results The results showed that the amount of ROS in the testicular tissue of male mice was higher only in the high-fat diet group. Also, there was no significant difference between the groups regarding eNOS testicular tissue in male mice. Conclusion A high-fat diet increases the production of reactive oxygen species in testicular tissue and is not affected by aerobic exercise. Also, neither exercise nor a high-fat diet had any effect on testicular eNOS. However, due to the limitations of this study and no evidence in this field, further studies are needed on cell phenotype, sperm fate, and identification of pathways involved in the occurrence of oxidative stress and subsequent effects of eNOS activation in testicular tissue in response to exercise and obesity.


Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4226-4236 ◽  
Author(s):  
Fausto Bogazzi ◽  
Francesco Raggi ◽  
Dania Russo ◽  
Mohammad Bohlooly-Y ◽  
Chiara Sardella ◽  
...  

Insulin resistance is a key marker of both obesity and GH excess. The purpose of the study was to assess the role of GH on p53-mediated insulin resistance of male mice with obesity due to a high-fat diet. C57BL/6J × CBA male mice fed on a high-fat diet (Obe) were studied; male mice fed a normal diet (Lean) or transgenic mice for bovine GH under the same genetic background (Acro) served as controls. The convergence of p53 and GH pathways was evaluated by Western blot. Obe mice had insulin resistance, which was sustained by a selective increased expression of p53 in adipose tissue. Normal insulin sensitivity was restored, and adipose p53 expression normalized when the GH pathway was blocked. Only the adipose p53 expression was sensitive to the GH blockage, which occurred through the p38 pathway. Adipose tissue of Obe mice had a coordinate overexpression of suppressors of cytokine signal 1–3 and signal transducers and activators of transcription-1, -3, and -5b, not different from that of Acro mice, suggesting an increased sensitivity of adipose tissue to GH. On the contrary, Lean mice were unaffected by changes of GH action. GH seems to be necessary for the increased adipose p53 expression and for insulin resistance of obese mice.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiani Wang ◽  
Christina Ortiz ◽  
Lindsey Fontenot ◽  
Riya Mukhopadhyay ◽  
Ying Xie ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bo-Htay ◽  
T Shwe ◽  
S Palee ◽  
T Pattarasakulchai ◽  
K Shinlapawittayatorn ◽  
...  

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants


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