Reduced SCD1 activity alters markers of fatty acid reesterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes

Dragos, Steven; Bergeron, Karl-F.; Desmarais, Frédérik; Suitor, Katherine; Wright, David C.; Mounier, Cathérine; Mutch, David M.

doi:10.1152/ajpcell.00097.2017

Cited by 26 publications

(17 citation statements)

References 34 publications

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“…The role of SCD1 is still controversial. SCD1 deficiency reduced lipogenesis and improved insulin sensitivity in adipose tissue ( Flowers and Ntambi, 2008 ; Ralston and Mutch, 2015 ); however, SCD1-deficient mice have altered fatty acid re-esterification and glyceroneogenesis in white adipose tissue ( Dragos et al, 2017 ). In Sq- and HH-Sq-treated cells, SCD1 gene expression was increased but did not show any aberrant lipid accumulation in adipocytes.…”

Section: Discussionmentioning

confidence: 99%

New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis

Ganbold

Ferdousi

Arimura

et al. 2020

Front. Cell Dev. Biol.

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Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, SIRT1 , PRKAA2 , and IRS1 . Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as PPARG , SREBF1 , and CEBPA , but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies.

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Section: Discussionmentioning

confidence: 99%

New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis

Ganbold

Ferdousi

Arimura

et al. 2020

Front. Cell Dev. Biol.

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“…Pck1 encodes the gluconeogenic enzyme PCK1, but in WAT, this enzyme is more glyceroneogenic [41]. SCD1 catalytically de-saturates fatty acyl–CoA substrates and also plays a role in glyceroneogenesis [42]. Targeted deletion of Scd1 in adipocytes impaired glyceroneogenesis in WAT, concomitant with the reduced other glyceroneogenesis markers, including the downregulation of Pck1 [42].…”

Section: Discussionmentioning

confidence: 99%

“…SCD1 catalytically de-saturates fatty acyl–CoA substrates and also plays a role in glyceroneogenesis [42]. Targeted deletion of Scd1 in adipocytes impaired glyceroneogenesis in WAT, concomitant with the reduced other glyceroneogenesis markers, including the downregulation of Pck1 [42]. Dysregulation of glyceroneogenesis in WAT induced by Pck1 mutation resulted in elevated TG levels in liver [43], impaired WAT glucose uptake and global glucose intolerance [43], a similar metabolic phenotype as seen in high dose NR-treated mice in our study.…”

Section: Discussionmentioning

confidence: 99%

High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet

et al. 2019

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Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor vitamin. The scarce reports on the adverse effects on metabolic health of supplementation with high-dose NR warrant substantiation. Here, we aimed to examine the physiological responses to high-dose NR supplementation in the context of a mildly obesogenic diet and to substantiate this with molecular data. An 18-week dietary intervention was conducted in male C57BL/6JRccHsd mice, in which a diet with 9000 mg NR per kg diet (high NR) was compared to a diet with NR at the recommended vitamin B3 level (control NR). Both diets were mildly obesogenic (40 en% fat). Metabolic flexibility and glucose tolerance were analyzed and immunoblotting, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were performed. Mice fed with high NR showed a reduced metabolic flexibility, a lower glucose clearance rate and aggravated systemic insulin resistance. This was consistent with molecular and morphological changes in eWAT, including sirtuin 1 (SIRT1)-mediated PPARγ (proliferator-activated receptor γ) repression, downregulated AKT/glucose transporter type 4 (GLUT4) signaling, an increased number of crown-like structures and macrophages, and an upregulation of pro-inflammatory gene markers. In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health.

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“…The rate of appearance of free fatty acids in the plasma is a function of the balance between lipolysis and reesterification in the adipose tissue [32]. Increased lipolysis and reduced reesterification have been observed in SCD1 knockout mice and after SCD1 inhibition in 3T3-L1 adipocytes [33]. Conversely, rosiglitazone treatment is known to increase SCD1 activity, reduce free fatty acid turnover, and improve peripheral insulin sensitivity, possibly by reducing fatty acid trafficking in the muscle [34,35].…”

Section: Discussionmentioning

confidence: 99%

Determinants of intramyocellular lipid accumulation in early childhood

et al. 2019

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Background/Objectives Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. Subjects/Methods This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. Results The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. Conclusion This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

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Reduced SCD1 activity alters markers of fatty acid reesterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes

Cited by 26 publications

References 34 publications

New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis

New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis

High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet

Determinants of intramyocellular lipid accumulation in early childhood

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