South Asian men have lower expression of IFN signalling genes in white adipose tissue and skeletal muscle compared with white men

Dam, Anke; Hanssen, Mark J. W.; Eenige, Robin van; Quinten, Edwin; Sips, Hetty C M; Hülsman, Cindy J. M.; Jazet, Ingrid M.; Lichtenbelt, Wouter D. van Marken; Ottenhoff, Tom H. M.; Haks, Mariëlle C.; Rensen, Patrick C.N.; Boon, Mariëtte R.

doi:10.1007/s00125-017-4427-8

Cited by 4 publications

(4 citation statements)

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“…In concordance, serum sclerostin levels positively correlated with skeletal muscle and adipose tissue insulin resistance in a hyperinsulinemic-euglycemic clamp study in human subjects with either normoglycemia or prediabetes [13]. Alternative mechanisms that may contribute to peripheral insulin resistance in South Asians are a pro-inflammatory status, including downregulation of genes involved in anti-inflammatory type 1 interferon signaling in WAT and skeletal muscle [35], lower adiponectin levels [36,37], as well as a lower skeletal muscle oxidative capacity [38] and cardiorespiratory fitness compared with white Caucasians [39].…”

Section: Discussionmentioning

confidence: 61%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

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Background: South Asians generally have an unfavourable metabolic phenotype compared with white Caucasians, including central obesity and insulin resistance. The Wnt protein family interacts with insulin signaling, and impaired Wnt signaling is associated with adiposity and type 2 diabetes mellitus. We aimed to investigate Wnt signaling in relation to insulin signaling in South Asians compared with white Caucasians. Methods: Ten Dutch South Asian men with prediabetes and overweight or obesity and 10 matched Dutch white Caucasians were included. Blood samples were assayed for the Wnt inhibitor sclerostin. Subcutaneous white adipose tissue (WAT) and skeletal muscle biopsies were assayed for Wnt and insulin signaling gene expression with quantitative reverse transcription polymerase chain reaction (Clinicaltrials.gov NCT02291458). Results: Plasma sclerostin was markedly higher in South Asians compared with white Caucasians (+65%, P<0.01). Additionally, expression of multiple Wnt signaling genes and key insulin signaling genes were lower in WAT in South Asians compared with white Caucasians. Moreover, in WAT in both ethnicities, Wnt signaling gene expression strongly positively correlated with insulin signaling gene expression. In skeletal muscle, WNT10B expression in South Asians was lower, but expression of other Wnt signaling and insulin signaling genes was comparable between ethnicities. Wnt and insulin signaling gene expression also positively correlated in skeletal muscle, albeit less pronounced. Conclusion: South Asian men with overweight or obesity and prediabetes have higher plasma sclerostin and lower Wnt signaling gene expression in WAT compared with white Caucasians. We interpret that reduced Wnt signaling could contribute to impaired insulin signaling in South Asians.

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Section: Discussionmentioning

confidence: 61%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

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“…South Asians and white Caucasians were matched for BMI. This study was conducted at the LUMC (the Netherlands) between November 2014 and August 2015 (18). Subjects underwent medical screening including an oral glucose tolerance test to identify individuals with impaired glucose tolerance according to the American Diabetes Association 2010 (19) and/or World Health Organization criteria.…”

Section: Participants and Study Designmentioning

confidence: 99%

“…The study procedures were described previously (18). In short, subjects were treated for 6 weeks with either l-arginine (9 g/d) (Argimax; Hankintatukku Oy, Karkkila, Finland) or placebo supplements (containing 70% microcrystalline cellulose, 29% maize starch, and 1% magnesium stearate) in a randomized double-blind crossover design, with a 4-week washout period.…”

Section: Study Proceduresmentioning

confidence: 99%

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Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight

Nahon

Kantae

Haan

et al. 2018

Obesity

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Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

Straat

Martínez-Téllez

Eyk

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context South Asians are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and progression of T2D, this factor is still underexplored in South Asians. Objective To study whether circulating mRNA transcripts of immune genes are different between South Asian versus Europid patients with T2D. Design Secondary analysis of two randomized controlled trials. Participants Dutch South Asian (n = 45; age: 55 ± 10 years, BMI: 29 ± 4 kg/m2) and Dutch Europid (n = 44; age: 60 ± 7 years, BMI: 32 ± 4 kg/m2) patients with T2D. Main outcome measures mRNA transcripts of 182 immune genes (microfluidic qPCR; Fluidigm Inc., USA) in fasted whole blood, ingenuity pathway analyses (Qiagen, USA). Results South Asians, compared to Europids, had higher mRNA levels of B cell markers [CD19, CD79A, CD79B, CR2, CXCR5, IGHD, MS4A1, PAX5; all FC > 1.3, FDR < 0.008] and IFN signaling genes [CD274, GBP1, GBP2, GBP5, FCGR1A/B/CP, IFI16, IFIT3, IFITM1, IFITM3, TAP1; all FC > 1.2, FDR < 0.05]. In South Asians, the IFN signaling pathway was the top canonical pathway (z-score 2.6, P < 0.001) and this was accompanied by higher plasma IFN-γ levels (FC = 1.5, FDR = 0.01). Notably, the ethnic difference in gene expression was larger for females [20/182 (11%)] than males [2/182 (1%)]. Conclusions South Asian patients with T2D show a more activated IFN signaling pathway compared to Europid patients with T2D, which is more pronounced in females than males. We speculate that a more activated IFN signaling pathway may contribute to the more rapid progression of T2D in South Asians compared with Europids.

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South Asian men have lower expression of IFN signalling genes in white adipose tissue and skeletal muscle compared with white men

Cited by 4 publications

References 6 publications

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight

Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

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