Current basis and future directions of zebrafish nutrigenomics

AbstractThis review investigates the current state of nutrigenomics in the zebrafish animal models. The zebrafish animal model has been used extensively in the study of disease onset and progression and associated molecular changes. In this review, we provide a synopsis of nutrigenomics using the zebrafish animal model. Obesity and dyslipidemia studies describe the genomics of dietary-induced obesity in relation to high-fat/high-calorie diets. Inflammation and cardiovascular studies describe dietary effects on the expression of acute inflammatory markers and resulting chronic inflammatory issues including atherosclerosis. We also evaluated the genomic response to bioactive dietary compounds associated with metabolic disorders. Carbohydrate metabolism and β-cell function studies describe the impacts of high-carbohydrate dietary challenges on nutritional programming. We also report tumorigenesis in relation to dietary carcinogen exposure studies that can result in permanent genomic changes. Vitamin and mineral deficiency studies demonstrate transgenerational genomic impacts of micronutrients in the diet and temporal expression changes. Circadian rhythm studies describe the relation between metabolism and natural temporal cycles of gene expression that impacts health. Bone formation studies describe the role of dietary composition that influences bone reabsorption regulation. Finally, this review provides future directions in the use of the zebrafish model for nutrigenomic and nutrigenetic research.

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Is There a Role of Coronary CTA in Primary Prevention? Current State and Future Directions

Current Atherosclerosis Reports ◽

10.1007/s11883-021-00943-2 ◽

2021 ◽

Vol 23 (8) ◽

Author(s):

Martin Bødtker Mortensen ◽

Michael J. Blaha

Keyword(s):

Primary Prevention ◽

Coronary Cta ◽

Future Directions ◽

Current State

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The role of gut microbiota and amino metabolism in the effects of improvement of islet β-cell function after modified jejunoileal bypass

Scientific Reports ◽

10.1038/s41598-021-84355-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cai Tan ◽

Zhihua Zheng ◽

Xiaogang Wan ◽

Jiaqing Cao ◽

Ran Wei ◽

...

Keyword(s):

Gut Microbiota ◽

Cell Function ◽

Body Weight Gain ◽

Fasting Blood Glucose ◽

Jejunoileal Bypass ◽

Β Cell ◽

Β Cell Function ◽

Branched Chain

AbstractThe change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet β-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet β-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet β-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet β-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

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Post-Transplant Diabetes Mellitus and Prediabetes in Renal Transplant Recipients: An Update

Nephron ◽

10.1159/000514288 ◽

2021 ◽

pp. 1-13

Author(s):

Ana Elena Rodríguez-Rodríguez ◽

Esteban Porrini ◽

Mads Hornum ◽

Javier Donate-Correa ◽

Raúl Morales-Febles ◽

...

Keyword(s):

Diabetes Mellitus ◽

Renal Transplant ◽

Cell Function ◽

Cell Damage ◽

Current Evidence ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Post Transplant ◽

Β Cell Function

Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20–30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.

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mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells

Journal of Endocrinology ◽

10.1530/joe-12-0351 ◽

2012 ◽

Vol 216 (1) ◽

pp. 21-29 ◽

Cited By ~ 21

Author(s):

Olivier Le Bacquer ◽

Gurvan Queniat ◽

Valery Gmyr ◽

Julie Kerr-Conte ◽

Bruno Lefebvre ◽

...

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Antagonistic Effect ◽

Dominant Negative ◽

Insulin Content ◽

Insulin Biosynthesis ◽

Direct Role ◽

Β Cell Function ◽

Glucose Stimulated Insulin Secretion

Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of β-cells. mTORC1 has long been known to impact β-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear. In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.

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Role of Sex Steroids in β Cell Function, Growth, and Survival

Trends in Endocrinology and Metabolism ◽

10.1016/j.tem.2016.08.008 ◽

2016 ◽

Vol 27 (12) ◽

pp. 844-855 ◽

Cited By ~ 39

Author(s):

Franck Mauvais-Jarvis

Keyword(s):

Sex Steroids ◽

Cell Function ◽

Β Cell ◽

Growth And Survival ◽

Β Cell Function

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Functional Role of Serotonin in Insulin Secretion in a Diet-Induced Insulin-Resistant State

Endocrinology ◽

10.1210/en.2014-1687 ◽

2014 ◽

Vol 156 (2) ◽

pp. 444-452 ◽

Cited By ~ 55

Author(s):

Kyuho Kim ◽

Chang-Myung Oh ◽

Mica Ohara-Imaizumi ◽

Sangkyu Park ◽

Jun Namkung ◽

...

Keyword(s):

Insulin Secretion ◽

Pancreatic Islets ◽

Cell Function ◽

Β Cell ◽

Pancreas Perfusion ◽

Insulin Resistant ◽

Β Cell Function ◽

Resistant State ◽

Insulin Resistant State

The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated. Here, we characterized the metabolic phenotypes of β-cell-specific Htr2b−/− (Htr2b βKO), Htr3a−/− (Htr3a knock-out [KO]), and β-cell-specific tryptophan hydroxylase 1 (Tph1)−/− (Tph1 βKO) mice on a high-fat diet (HFD). Htr2b βKO, Htr3a KO, and Tph1 βKO mice exhibited normal glucose tolerance on a standard chow diet. After 6 weeks on an HFD, beginning at 4 weeks of age, both Htr3a KO and Tph1 βKO mice developed glucose intolerance, but Htr2b βKO mice remained normoglycemic. Pancreas perfusion assays revealed defective first-phase insulin secretion in Htr3a KO mice. GSIS was impaired in islets isolated from HFD-fed Htr3a KO and Tph1 βKO mice, and 5-HT treatment improved insulin secretion from Tph1 βKO islets but not from Htr3a KO islets. Tph1 and Htr3a gene expression in pancreatic islets was not affected by an HFD, and immunostaining could not detect 5-HT in pancreatic islets from mice fed an HFD. Taken together, these results demonstrate that basal 5-HT levels in β-cells play a role in GSIS through Htr3, which becomes more evident in a diet-induced insulin-resistant state.

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