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

Expansion of Perivascular Adipose Tissue (PVAT), a major regulator of vascular function through paracrine signaling, is directly related to the ...

Michigan State University

Excessive rates of demand lipolysis in the adipose tissue (AT) during periods of negative energy balance (NEB) are associated with increased susceptibility to disease and limited lactation performance. Lipolysis induces a remodeling process within AT that is characterized by an inflammatory response, cellular proliferation, and changes in the extracellular matrix (ECMT). The adipose tissue macrophage (ATM) is a key component of the inflammatory response. Infiltration of ATM-forming cellular aggregates was demonstrated in transition cows, suggesting that ATM trafficking and phenotype changes may be associated with disease. However, it is currently unknown if ATM infiltration occurs in dairy cows only during NEB states related to the transition period or also during NEB-induced lipolysis at other stages of lactation. The objective of this study was to evaluate changes in ATM trafficking and inflammatory phenotypes, and the expression of genetic markers of AT remodeling in healthy late-lactation cows during feed restriction-induced NEB. After a 14-d (d -14 to d -1) preliminary period, Holstein cows were randomly assigned to 1 of 2 feeding protocols, ad libitum (AL) or feed restriction (FR), for 4 d (d 1-4). Caloric intake was reduced in FR to achieve a targeted energy balance of -15 Mcal/d of net energy for lactation. Omental and subcutaneous AT samples were collected laparoscopically to harvest stromal vascular fraction (SVF) cells on d -3 and 4. The FR induced a NEB of -14.1±0.62 Mcal/d of net energy for lactation, whereas AL cows remained in positive energy balance (3.2±0.66 Mcal/d of NEL). The FR triggered a lipolytic response reflected in increased plasma nonesterified fatty acids (0.65±0.05 mEq/L on d 4), enhanced phosphorylation of hormone sensitive lipase, and reduced adipocyte diameter. Flow cytometry and immunohistochemistry analysis revealed that on d 4, FR cows had increased numbers of CD172a(+), an ATM (M1 and M2) surface marker, cells in SVF that were localized in aggregates. However, FR did not alter the number of SVF cells expressing M1 markers (CD14 and CD11c) or M2 markers (CD11b and CD163). This finding contrasts with the predominately M1 phenotype observed previously in ATM from clinically diseased cows. No changes were observed in the expression of ECMT-related or cell proliferation markers. In summary, an acute 4-d lipolytic stimulus in late-lactation dairy cows led to ATM infiltration with minimal changes in inflammatory phenotype and no changes in ECMT. These results underscore that physiological changes related to parturition, the onset of lactation, extended periods of lipolysis, or a combination of these can induce intense AT remodeling with enhanced ATM inflammatory phenotype expression that may impair the metabolic function of AT in transition dairy cattle.

Adipose tissue remodeling in late-lactation dairy cows during feed-restriction-induced negative energy balance.

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.

Kyan Thelen

Department of Large Animal Clinical Sciences

Michigan State University

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

Kyan Thelen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Large Animal Clinical Sciences

Michigan State University

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

Department of Large Animal Clinical Sciences