Ethnic Differences in Pancreatic Fat Accumulation and Its Relationship With Other Fat Depots and Inflammatory Markers

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species.

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Ectopic fat: the true culprit linking obesity and cardiovascular disease?

Thrombosis and Haemostasis ◽

10.1160/th13-04-0285 ◽

2013 ◽

Vol 110 (10) ◽

pp. 651-660 ◽

Cited By ~ 31

Author(s):

Mariangela Morelli ◽

Melania Gaggini ◽

Giuseppe Daniele ◽

Paolo Marraccini ◽

Rosa Sicari ◽

...

Keyword(s):

Cardiovascular Disease ◽

Subcutaneous Fat ◽

Protective Mechanism ◽

Ectopic Fat ◽

Fat Accumulation ◽

Fat Depots ◽

Excess Adiposity ◽

Specific Organ ◽

The Impact ◽

Organ Dysfunctions

SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardiometabolic diseases.

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Independent association between prediabetes and future pancreatic fat accumulation: a 5-year Japanese cohort study

Journal of Gastroenterology ◽

10.1007/s00535-017-1422-2 ◽

2017 ◽

Vol 53 (7) ◽

pp. 873-882 ◽

Cited By ~ 3

Author(s):

Hajime Yamazaki ◽

Shinichi Tauchi ◽

Miho Kimachi ◽

Mitsuru Dohke ◽

Nagisa Hanawa ◽

...

Keyword(s):

Cohort Study ◽

Fat Accumulation ◽

Japanese Cohort ◽

Pancreatic Fat ◽

Independent Association

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The Link between Obesity and Inflammatory Markers in the Development of Type 2 Diabetes in Men of Black African and White European Ethnicity

Nutrients ◽

10.3390/nu12123796 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3796

Author(s):

Olah Hakim ◽

Oluwatoyosi Bello ◽

Meera Ladwa ◽

Janet L. Peacock ◽

A. Margot Umpleby ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Ethnic Differences ◽

Inflammatory Markers ◽

Normal Glucose Tolerance ◽

West African ◽

Black African ◽

Normal Glucose ◽

The Relationship

In this study, we aimed to assess ethnic differences in visceral (VAT), deep subcutaneous (dSAT), and superficial subcutaneous (sSAT) adipose tissue and their relationships with inflammatory markers between white European (WE) and black West African (BWA) men with normal glucose tolerance (NGT) and type 2 diabetes (T2D). Forty-two WE (23 NGT/19 T2D) and 43 BWA (23 NGT/20 T2D) men underwent assessment of plasma inflammatory markers using immunoassays alongside Dixon magnetic resonance imaging to quantify L4-5 VAT, dSAT and sSAT. Despite no ethnic differences in sSAT and dSAT, BWA men exhibited lower VAT (p = 0.002) and dSAT:sSAT (p = 0.047) than WE men. Adiponectin was inversely associated with sSAT in WE (p = 0.041) but positively associated in BWA (p = 0.031) men with T2D. Interleukin-6 (IL-6) was associated with VAT in WE but not in BWA men with NGT (WE: p = 0.009, BWA: p = 0.137) and T2D (WE: p = 0.070, BWA: p = 0.175). IL-6 was associated with dSAT in only WE men with NGT (WE: p = 0.030, BWA: p = 0.833). The only significant ethnicity interaction present was for the relationship between adiponectin and sSAT (Pinteraction = 0.003). The favourable adipose tissue distribution and the weaker relationships between adiposity and inflammation in BWA men suggest that adipose tissue inflammation may play a lesser role in T2D in BWA than WE men.

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Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002034 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002034

Author(s):

Meera Ladwa ◽

Oluwatoyosi Bello ◽

Olah Hakim ◽

Fariba Shojaee-Moradie ◽

Maria Linda Boselli ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Beta Cell ◽

Ethnic Differences ◽

Beta Cell Function ◽

Cell Function ◽

White Men ◽

Black And White ◽

Pancreatic Fat ◽

Postprandial Insulin

IntroductionIt is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry.Research design and methodsA cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity.ResultsPostprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) × 103 vs 56.4 (95% CI 48.9 to 63.8) × 103 pmol/m2 body surface area × 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity.ConclusionsEthnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry.

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Abstract 196: Genetically Modified Human Mesenchymal Stromal Cells (MSCs) Help Improve Glucose Homeostasis by Reducing Inflammation and Promotes Browning of Visceral Fat

Circulation Research ◽

10.1161/res.121.suppl_1.196 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Sabyasachi Sen ◽

Cleyton Domingues ◽

Nabanita Kundu ◽

Neeki Ahmadi

Keyword(s):

Mrna Expression ◽

Glucose Homeostasis ◽

Visceral Fat ◽

Inflammatory Markers ◽

Tolerance Test ◽

Mice Model ◽

Fat Depots ◽

Insulin Tolerance ◽

Omental Fat

Background: MSCs are multipotent cells that can home-in to a site of inflammation. Upregulation of specific antioxidants in MSCs reduces intracellular inflammation and ROS formation in a hyperglycemic condition. Hypothesis: Antioxidant over-expressed MSCs will reach fat depots, reduce local & systemic inflammation and improve glucose homeostasis in diet-induced obese (DIO, 60% and 45% fat diet) hyperglycemic mouse models. Methods: We used GFP-containing adenoviral constructs to upregulate intracellular (SOD1, SOD2, Catalase) and extracellular (SOD3) antioxidants in human adipose-derived MSCs. The modified MSCs were delivered in DIO mice. Results: In-vitro, SOD2 (mitochondrial anti-oxidant) upregulation showed reduced inflammatory markers IL6 and TNFa mRNA while PCG1A mRNA (a gene upstream of UCP1), upregulated. SOD2 upregulated MSC delivery in both DIO models demonstrated improved glucose tolerance test (GTT) at week 4 compared to SOD1-MSC and Null-MSC (control). Catalase-MSC delivery not only improved GTT but also improved insulin tolerance test (ITT) in 60% DIO mice. Interestingly, RT-PCR of pericardial fat showed significant increases in mRNA expression of both UCP1 (25-100,000-fold) and PRDM-16 (2-10-fold) in both DIO mice models that received antioxidants upregulated MSCs, compared to mice receiving Null MSCs. For omental fat, an increase in mRNA expression of UCP1 was observed in 60% fat DIO mice (1,000-6000 fold) for SODs 1-3 and catalase, while for 45% DIO mice only those receiving SOD1 & SOD2 upregulated MSCs presented UCP1 mRNA upregulation (1,000 to 11,000-fold). Omental Fat histology showed less hyperplastic fat with SOD2 and Catalase-MSCs. UCP1 staining of omental fat was also positive with SOD2-MSC. Inflammatory molecules such as IL-6 and TNF alpha levels by ELISA, were reduced with SOD2-MSC in 60% DIO mice model. Conclusion: We conclude that delivery of antioxidant upregulated MSCs to the inflamed adipocyte depots in diabetic DIO models appear to upregulate UCP1 and PRDM-16 in visceral fat while reducing systemic inflammatory markers, which may explain improvements noted in GTT and ITT. Delivery of modified MSC is a novel & robust therapeutic tool that improves glucose homeostasis in diet induced diabetes.

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