Influence of adipocyte size and adipose depot on the number of adipose tissue macrophages and the expression of adipokines in dairy cows at the end of pregnancy

Abstract

The aim of this study was to determine the number of adipose tissue macrophages (ATM) and the mRNA expression of adipokines [adiponectin (ADIPOQ), leptin (LEP), interleukin 6 (IL6), tumor necrosis factor (TNF), and interleukin 10 (IL10)] in different adipose depots from cows with a variable body condition score (BCS) at the end of the dry period. We hypothesized that the number of ATM and the expression of these adipokines depend on adipocyte size and the anatomical location of the adipose depot. Subcutaneous, omental, mesenteric, perirenal, and intrapelvic adipose tissue samples were taken immediately after euthanasia of 10 Holstein Friesian dairy cows (upcoming parity 2 to 5, age 3.9 ± 1.4 yr; mean ± standard deviation) at the end of pregnancy (actual days of pregnancy at the moment of euthanasia: 269 ± 5 d). During the dry period, all animals received similar diets to meet but not exceed requirements. Five animals were considered to have a normal BCS (2.5-3.5) and 5 animals were considered to be over-conditioned (BCS = 3.75-5). Body weight of the animals at the moment of euthanasia was 717 ± 77 kg. Expression of the different genes was determined by reverse transcription quantitative real-time PCR. Adipocyte size was determined by measuring the area of 100 adipocytes on histological sections. Average adipocyte area was 10,475 ± 1,019, 8,500 ± 780, 10,383 ± 1,227, 11,466 ± 1,039, and 11,087 ± 1,632 µm for the subcutaneous, mesenteric, omental, intrapelvic, and perirenal adipose depot, respectively. Immunohistochemistry using anti-bovine CD172a antibodies was performed to determine the proportion of ATM (the number of CD172a-positive cells per 100 adipocytes, given as a percentage). Expression of LEP, IL6, and TNF was positively associated with adipocyte size, whereas no association could be detected between ADIPOQ and IL10 with the size of the adipocytes. The omental adipose depot was especially infiltrated with ATM (1.92 ± 0.55, 1.10 ± 0.33, and 8.28 ± 2.24% for the subcutaneous, mesenteric, and omental adipose depot, respectively). The proportion of ATM was positively associated with the size of the adipocytes in the omental and mesenteric adipose depot. Expression of ADIPOQ, LEP, IL6, TNF, and IL10 differed among depots, which suggests differences in inflammatory characteristics depending on the anatomical location of depots. In conclusion, the results of the present study confirm the adipose tissue as a potential source of inflammatory mediators and demonstrate ATM infiltration, especially in the omental adipose depot.

Metabolic Stress in the Transition Period of Dairy Cows: Focusing on the Prepartum Period

“…Dairy cow over-conditioning at the end of pregnancy is associated with a plethora of metabolic, digestive, infectious, and reproductive conditions known as the "fat cow syndrome" [66,67]. The results and discussion presented in the present section represent a summary of studies performed by our research group [68][69][70][71][72][73]. For these studies, ten clinically healthy pregnant multiparous Holstein-Friesian cows were selected at the beginning of the dry period based on their BCS and classified as normal-conditioned (2.5-3.5; n = 5) or over-conditioned (3.75-5; n = 5).…”

“…The latter allowed us to eventually confirm the results found in vivo by in vitro tests on the harvested tissues following euthanasia. Detailed methodological data associated with management conditions, diets, and cow-related information are presented in the publications derived from these experimental cows [68][69][70][71][72][73]. Here, we synthesize the most relevant data found in terms of normal-and over-conditioning at the end of pregnancy on insulin resistance, adipose tissue physiology, and the liver transcriptomics profile.…”

“…Interestingly, it was described that macrophages infiltrated within the adipose tissue are the main producers of the fat-derived pro-inflammatory cytokines in obese humans [88][89][90]. Depreester et al [72] tested this hypothesis in a dairy cow model by determining the counts of adipose tissue macrophages (ATM) and the mRNA profile of TNF-α and IL-6 (among other adipokines) in subcutaneous and omental adipose depots from over-and normal-conditioned cows at the end of pregnancy. They found that over-conditioned cows had larger adipocytes, as demonstrated by the strong correlation between BCS and adipocyte size.…”

Transcriptomic profiling of adipose tissue inflammation, remodeling, and lipid metabolism in periparturient dairy cows (Bos taurus)

“…Zhang and colleagues characterized lipolysis induced IL6 secretion as a hormone-sensitive lipase activation-dependent event in rodents [ 44 ]. In dairy cows, postpartum AT IL6 upregulation is a commonly described transcriptomic finding [ 45 ]. Both the macrophage inflammatory protein 2-alpha, encoded by CXCL2, and monocyte chemoattractant protein-1, encoded by CCL2, are promoters of macrophage infiltration into AT [ 46 ].…”

Immune cell populations residing in mesenteric adipose depots and mesenteric lymph nodes of lean dairy cows

“…Failure of homeorhetic regulation of metabolic activity during the postpartum period leads to dysregulated metabolic states and increased risk of metritis, ketonemia, displaced abomasum, retained placenta, and susceptibility to infection (Ospina et al, 2010). A signature event associated with insulin resistance in adipose depots of obese monogastrics is the induction of inflammation (Weisberg et al, 2003;Xu et al, 2003;Deiuliis et al, 2011) following reductions in resident regulatory or anti-inflammatory immune cells (Osborn and Olefsky, 2012;Mathis, 2013;Panduro et al, 2016) that normally counterbalance tissue inflammation (Mukesh et al, 2010;Vatier et al, 2012;Depreester et al, 2018). In contrast to monogastrics, results in bovines indicate that substantial numbers (Contreras et al, 2015) or trace amounts (Akter et al, 2012) of inflammatory cell infiltrates appear in postpartum adipose depots of overconditioned dairy cows.…”