Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice

Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

doi:10.1016/j.jcjd.2016.06.003

Cited by 25 publications

(16 citation statements)

References 47 publications

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“…A deep understanding of cross-talk between muscle cells and intramuscular adipocytes could be utilized to improve meat quality in chickens. In humans, excessive intracellular lipid accumulation in skeletal muscle is associated with some metabolic diseases such as insulin resistance and type 2 diabetes [ 61 – 63 ]. The data suggest that some factor secreted by adipocytes induced intracellular lipid accumulation in muscle cells, which provide important insights for livestock meat quality and human metabolic disease.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens

et al. 2018

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BackgroundSkeletal muscle satellite cells (MSC) are crucial for postnatal growth and regeneration of skeletal muscle. An interaction exists between MSC and intramuscular preadipocytes (IMPA). This study is the first to investigate the effects of IMPA on MSC in chickens and unveil the molecular mechanisms by transcriptome analysis.ResultsPrimary MSC and IMPA were isolated from the pectoralis major muscle of 7-day-old chickens. After both cell types reached confluence, MSC were cultured alone or co-cultured with IMPA for 2 or 4 d. MSC treated for 2 d were subjected to RNA-seq. A total of 1653 known differentially expressed genes (DEG) were identified between co-cultured and mono-cultured MSC (|log2 FC| ≥ 1, FDR < 0.01). Based on Gene Ontology analysis, 48 DEG related to muscle development were screened, including the key genes MYOD1, MYOG, PAX7, and TMEM8C. The 44 DEG related to lipid deposition included the key genes CD36, FABP4, ACSBG2, CYP7A1 and PLIN2. Most of the DEG related to muscle development were downregulated in co-cultured MSC, and DEG related to lipid deposition were upregulated. Immunofluorescence of MHC supported IMPA impeding differentiation of MSC, and Oil Red O staining showed concurrent promotion of lipid deposition. Pathway analysis found that several key genes were enriched in JNK/MAPK and PPAR signaling, which may be the key pathways regulating differentiation and lipid deposition in MSC. Additionally, pathways related to cell junctions may also contribute to the effect of IMPA on MSC.ConclusionsThe present study showed that IMPA impeded differentiation of MSC while promoting their lipid deposition. Pathway analysis indicated that IMPA might inhibit differentiation via the JNK/MAPK pathway, and promote lipid deposition via the PPAR pathway. This study supplies insights into the effect of IMPA on MSC, providing new clues on exposing the molecular mechanisms underlying the interplay between skeletal muscle and intramuscular fat in chickens.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5209-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens

et al. 2018

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“…This may suggest that chronic stress further exacerbates the fructose-mediated induction of 11β-HSD1 and local glucocorticoid effects on lipolysis and adipogenesis. A recent study with mice that were fed a high-fructose diet for 60 days found elevated glucocorticoid levels in liver and adipose tissue as well as enhanced GR in the nucleus and activation of its target genes [144]. Plasma FFA, TG, insulin, and glucose were increased while hepatic glycogen was decreased.…”

Section: Effect Of Fructose On 11β-hsd1 Expression and Activitymentioning

confidence: 99%

Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic Syndrome

et al. 2017

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The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β-HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β-HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome.

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“…Similarly, mifepristone is reported to reduce glucose levels by 50% along with suppression of gluconeogenesis enzymes in db/db mice (Friedman et al, ). Efficacy of mifepristone against insulin resistance and dyslipidemia has been demonstrated in high‐fructose fed rodents (Priyadarshini & Anuradha, ). More importantly, mifepristone is now approved for treating hyperglycemia in Cushing's syndrome patients.…”

Section: Resultsmentioning

confidence: 99%

Antiglucocorticoid potential of nutraceuticals: In silico molecular docking and in vitro assessment

et al. 2018

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Glucocorticoid hormones are known for their diabetogenic effects. We explored the antiglucocorticoid potential of andrographolide, curcumin, diosgenin, ellagic acid, genistein, gibberellin A3, kaempferol, quercetin, resveratrol, and silibinin using molecular docking simulations and cell-based studies. Docking simulations accurately predicted the binding pose of mifepristone as revealed by appreciable superimposition of predicted pose with that of the crystal data. With the exception of diosgenin, all tested nutraceuticals were predicted to occupy the inhibitor site on glucocorticoid receptor in silico. Cell-based studies performed with H4-IIE-C3 cells revealed that curcumin, genistein, kaempferol, and quercetin possess the propensity to antagonize dexamethasone-induction of tyrosine aminotransferase activity. Our work suggests that curcumin, genistein, kaempferol, and quercetin exhibit antiglucocorticoid activity in vitro. Practical applicationsThis work shows that curcumin, genistein, kaempferol, and quercetin exhibit antiglucocorticoid activity, although it remains to be understood whether the antagonism reported here is mediated by direct interaction with the receptor or due to secondary mechanisms. Our work establishes the basis for exploring the relevance of glucocorticoid antagonism in antidiabetic potential of curcumin, genistein, kaempeferol, and quercetin in vivo. Our work also provides a scientific rationale for utilizing curcumin, genistein, kaempeferol, and quercetin as ingredients for development of functional foods for dietary management of type 2 diabetes.

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Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice

Cited by 25 publications

References 47 publications

Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens

Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens

Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic Syndrome

Antiglucocorticoid potential of nutraceuticals: In silico molecular docking and in vitro assessment

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