DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression

Abu‐Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Tiss, Ali; Khadir, Abdelkrim; Kavalakatt, Sina; Warsame, Samia; Dehbi, Mohammed; Behbehani, Kazem; Abubaker, Jehad

doi:10.1038/srep14448

Cited by 29 publications

(54 citation statements)

References 46 publications

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“…For example, we have previously showed that exercise is an important regulator of DNAJB3 protein a member of the HSP40 protein family that has been shown to be downregulated by obesity and upregulated after physical exercise. Its overexpression has been associated with improvement in glucose uptake and insulin signalling [29, 33]. In this study, we show that ANGPTL7 is downregulated after physical exercise in plasma and circulation.…”

Section: Discussionsupporting

confidence: 57%

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise

et al. 2017

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ObjectiveANGPTL7 is a member of the Angiopoietin-like (ANGPTL) protein family that is composed of eight proteins (1–8). Increasing evidence is associating ANGPTL proteins to obesity and insulin resistance. The biological role of ANGPTL7 is yet to be understood except for a recently proposed role in the pathophysiology of glaucoma. This study was designed to shed light on the function of ANGPTL7 in obesity and its modulation by physical exercise as well as its potential association with lipid profile.MethodsA total of 144 subjects were enrolled in this study and finished three months of physical exercise. The participants were classified based on their BMI, 82 subjects were non-obese and 62 obese. ANGPTL7 levels in plasma and adipose tissue were measured by ELISA, RT-PCR and immunohistochemistry.ResultsIn this study, we showed that ANGPTL7 level was increased in the plasma of obese subjects (1249.05± 130.39 pg/mL) as compared to non-obese (930.34 ± 87.27 pg/mL) (p-Value = 0.032). ANGPTL7 Gene and protein expression levels in adipose tissue also showed over two fold increase. Physical exercise reduced circulating level of ANGPTL7 in the obese subjects to 740.98± 127.18 pg/mL, (p-Value = 0.007). ANGPTL7 expression in adipose tissue was also reduced after exercise. Finally, ANGPTL7 circulating level showed significant association with TG level in the obese subjects (R2 = 0.183, p-Value = 0.03).ConclusionIn conclusion, our data shows for the first time that obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia.

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Section: Discussionsupporting

confidence: 57%

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise

et al. 2017

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“…Blood samples were collected in a vacutainer EDTA tube where the plasma was separated by centrifugation at 400× g for 10 min. The plasma was then aliquoted and stored at −80 °C until it was assayed as previously reported [ 50 , 62 , 63 ]. Blood pressure was measured using an Omron HEM-907XL digital sphygmomanometer.…”

Section: Methodsmentioning

confidence: 99%

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

et al. 2020

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Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. Methods: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. Results: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth’s sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. Conclusion: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients.

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“…Blood samples were collected in vacutainer EDTA tubes that were centrifuged to collect plasma samples which in turn were aliquoted and stored at −80 °C until assayed as described previously [ 22 – 24 ]. Subcutaneous adipose tissue (SAT) biopsies were obtained from the periumbilical area by surgical biopsy after a local anaesthesia as described previously [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D

et al. 2016

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BackgroundHypertriglyceridemia is associated with increased risk for cardiovascular diseases and type 2 diabetes (T2D). Angiopoietin like proteins particularly 3, 4 and recently 8 are well established regulators of plasma triglyceride level through regulating the activity of lipoprotein lipase. Plasma level and association between ANGPTL3, 4 and 8 is not well established in human subjects. This study was designed to establish the level of these proteins in plasma and adipose tissues and investigate the association between ANGPTL8 with ANGPTL3 and 4 in T2D and non-diabetics subjects.MethodsA total of 235 subjects were enrolled in this study, 144 non-diabetics and 91 T2D. ANGPTL 3, 4 and 8 levels were measured in plasma by ELISA and using real time RT-PCR in adipose tissues.ResultsIn this study, we showed that ANGPTL3, 4 and 8 were higher in T2D subjects. Dividing the non-diabetic subjects according to their BMI showed higher level of ANGPTL3, 4 and 8 in obese subjects compared to non-obese subjects. No significant difference was observed between the T2D subjects. ANGPTL8 was showed positive correlation with ANGPTL3 in the non-diabetic subjects in the non-obese (r = 0.2437, p-Value = 0.0543) and obese subjects (r = 0.418, p-Value = 0.0125). No association was observed in the T2D subjects. On the other hand, ANGPTL4 was positively associated with the obese subjects in both the non-diabetics (r = 0.3322, p-Value = 0.0316) and the obese T2D subjects (r = 0.3161, p-Value = 0.0211).ConclusionIn conclusion, our data shows that ANGPTL3, 4 and 8 are increased in obesity and T2D. ANGPTL8 associates with ANGPTL3 in the non-diabetic subjects while it associated more with ANGPTL4 in the obese and T2D subjects. Taken together, this data highlight the role of these proteins in metabolic diseases and how they interact with each other’s under different physiological and pathophysiological conditions.

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DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression

Cited by 29 publications

References 46 publications

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D

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