The distribution and adipogenic potential of perivascular adipose tissue adipocyte progenitors is dependent on sexual dimorphism and vessel location

Abstract

There are sex associated differences in the risk for cardiovascular comorbidities in obesity and metabolic syndrome. A common clinical finding in these diseases is the expansion of perivascular adipose tissues (PVAT) which is associated with alterations in their role as regulators of vessel function. PVAT hyperplasia and hypertrophy are dependent on the biology of populations of adipocyte progenitor cells (APC). It is currently unclear if PVAT enlargement diverges between males and females and the mechanisms linking APC biology with sexual dimorphism remain poorly understood. This study tested the hypothesis that vessel location and sexual dimorphism affect the distribution and adipogenic capacity of APC in cardiovascular disease risk relevant PVAT sites. PVAT from thoracic aorta (aPVAT) and mesenteric resistance arteries (mPVAT) was collected from 10‐week‐old female and male Sprague–Dawley rats. Differences in APC distribution in stromal vascular fraction cells from PVAT were determined. APC were defined as cells expressing CD34, CD44, and platelet derived growth factor α. In both sexes aPVAT had fewer APC compared to mPVAT and perigonadal adipose tissue (GON). Sex‐related differences were observed in the expression of CD34, where females had fewer CD34+ cells in PVATs. APC proliferation and adipogenic capacity in vitro were not affected by sex. However, APC from aPVAT had a lower proliferation capacity compared to mPVAT. These data demonstrate that the distribution of APC within PVAT exhibits sexual dimorphism and is affected by anatomical location.

Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting

“…These surface proteins were previously identified on APC with high proliferation rates and the potential to differentiate into white or brown adipocytes in various adipose depots 14,15 . By selecting cells based on these specific markers, we were able to isolate similar APC populations from multiple adipose depots that match the adipocyte phenotype that is observed in the PVAT selected 13 . In our experiments we improved APC differentiation by supplementing the growth factor BMP4.…”

Fetuin-A: A negative acute-phase protein linked to adipose tissue function in periparturient dairy cows

“…Stromal vascular fraction cells were obtained by collagenase digestion of tailhead subcutaneous AT collected from nonlactating nongestating dairy cows (n = 6) at a local abattoir as described previously (Contreras et al, 2015). Stromal vascular fraction cells were cultured in basal medium containing Dulbecco's modified Eagle's medium: F12 (Corning, Corning, NY), 10% fetal bovine serum (Corning), 2 mmol/L of l-glutamine (Corning), 1% (vol/vol) antibiotic-antimycotic (Corning), 44.05 mmol/L of sodium bicarbonate (Sigma-Aldrich, St. Louis, MO), 100 μmol/L of ascorbic acid (Sigma-Aldrich), 33 μmol/L of biotin (Sigma-Aldrich), 17 μmol/L of pantothenate (Sigma-Aldrich), and 20 mmol/L of HEPES (Corning) with replacement every 2 d as described previously (Contreras et al, 2016a). Preadipocytes were obtained by outgrowth of plastic adherent cells from the stromal vascular fraction cells after 2 serial passages.…”

Sex differences in regulation of adipose tissue

“…путем реализации двух основных механизмов -увеличения размера адипоцитов (гипертрофия) или их количества (гиперплазия) за счет рекрутирования предшественников адипоцитов -преадипоцитов из стромальной васкулярной фракции (SVF) [32]. Когда жировые клетки достигают предела своих размеров и не могут больше накапливать жир, включаются механизмы развития метаболических нарушений [33].…”

“…На сегодня гиперплазия адипоцитов считается защитным вариантом реакции ЖТ на потребление жира и калорий, поскольку снижает вероятность эктопического отложения жира. Гиперплазия адипоцитов ведет к появлению малых адипоцитов, которые не только более чувствительны к инсулину, но также обладают большей способностью к накоплению жира [17,32]. Есть доказательства того, что развитие осложнений ожирения является результатом гипертрофии адипоцитов [14,34].…”

“…Различия механизмов отложения жира в ВЖТ и ПЖТ закономерно связаны с эстрогенами. Как оказалось, эстрогены, рецепторы к которым превалируют в ПЖТ, влияют на процесс гиперплазии адипоцитов, стимулируя формирование молодых адипоцитов из преадипоцитов SVF [16,23,32]. Кроме того, эстрогены являются стимуляторами роста сосудов через прямую активацию экспрессии VEGF и рецепторов к этому фактору роста, а также Са2+-независимыми активаторами eNOS, фермента, обеспечивающего продукцию эндотелиоцитами оксида азота, обеспечивающего поддержание оптимального кровотока [12,21].…”