ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

Abstract

Supplemental Material can be found at: 2338 Journal of Lipid Research Volume 56, 2015ATMs and that Abcg1 plays a key role in modulating ATM cholesterol levels in obesity and acute weight loss.ATMs were collected from mice for which the myeloid cells had been replaced by bone marrow transplantation (BMT) from Abcg1 Ϫ / Ϫ mice and from WT mice undergoing autologous BMT. We found that Abcg1 expression affected the steady-state cholesterol levels of ATMs, with Abcg1ATMs having the highest total cholesterol content. Other sterol species were not evaluated due to limitations in ATM cell quantities. We found that the ratio of M1 to M2 ATMs was altered with loss of Abcg1 expression, and that Abcg1 was most highly expressed by M2 rather than proinfl ammatory M1 macrophages suggesting that M2 cells have a unique role in adipose tissue sterol homeostasis. Overall, this study identifi es ABCG1 as an important protein determining the relative levels of ATMs and cholesterol metabolism especially in M2 macrophages. Understanding the contribution of ABCG1 to ATM cholesterol homeostasis may provide new information for controlling obesity, weight loss, and related disorders such as lung, liver, and gallbladder diseases ( 38-40 ). MATERIALS AND METHODS MiceIsogenic WT C57BL/6 mice were purchased from the Jackson Laboratory (Bar Harbor, ME; #000664). ABCG1 knockout ( Abcg1 Ϫ / Ϫ ) mice on a C57BL/6 background were generated as previously described ( 41 ). BMT was conducted using C57BL/6 male mice as acceptors of either C57BL/6 bone marrow cells (WT-BMT) or cells from Abcg1 Ϫ / Ϫ mice ( Abcg1 Ϫ / Ϫ BMT) using procedures as described below. Femurs taken from Abcg1Ϫ / Ϫ mice were placed in PBS and sent overnight on ice from the University of California, Los Angeles to the University of Washington where bone marrow cells were isolated. In addition, C57BL/6 male mice raised at the University of Washington (three to four generations from the Jackson Laboratory) were used as a reference strain for measures of body composition. All mice were housed in pathogen-free conditions, in a temperature-and humidity-controlled environment (12 h light/dark cycle). Animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee of University of Washington. Study designBMT was performed essentially as described ( 42 ). Briefl y, male C57BL/6 mice (WT) at 13 weeks of age were irradiated (950 rads) and then engrafted with either WT or Abcg1 Ϫ / Ϫ bone marrow cells (5 × 10 6 cells/mouse; n = 20 in each group) by retroorbital injection. Mice were maintained on pelleted rodent chow (LabDiet 5053; Purina Mills, St. Louis, MO) and acidifi ed water with neomycin (X-gen Pharmaceuticals, Big Flats, NY) for 4 weeks of recovery. Mice were then fed a high-fat diet (HFD) [D12492; Research Diets Inc., New Brunswick, NJ; 60% kcal (primarily lard) and 20% kcal carbohydrate (maltodextrin 10 and sucrose)] for 13 weeks. Mice were then randomly assigned to one of two groups for another 3 weeks of either continued ad libitum HFD feeding or to...

Basis of bone metabolism around dental implants during osseointegration and peri‐implant bone loss

“…In addition, obesity induces a systemic inflammation condition with high levels of circulating cytokines and increased production of monocytes, neutrophils and adipose tissue macrophages . These cytokines and the accumulation of cholesterol in macrophages can alter the ratio of M1/M2 macrophages promoting an M1 proinflammatory environment thereby increasing the numbers of monocytes/macrophages in circulation …”

“…96,100,[103][104][105] In addition, obesity induces a systemic inflammation condition with high levels of circulating cytokines and increased production of monocytes, neutrophils 106,107 and adipose tissue macrophages. 108,109 These cytokines and the accumulation of cholesterol in macrophages can alter the ratio of M1/M2 macrophages promoting an M1 proinflammatory environment thereby increasing the numbers of monocytes/macrophages in circulation. 108,110 The influence of obesity and increased levels of cholesterol and triglycerides have been extensively described in the medical field but the effect of hyperlipidemia on dental implant osseointegration has not yet been fully elucidated.…”

“…108,109 These cytokines and the accumulation of cholesterol in macrophages can alter the ratio of M1/M2 macrophages promoting an M1 proinflammatory environment thereby increasing the numbers of monocytes/macrophages in circulation. 108,110 The influence of obesity and increased levels of cholesterol and triglycerides have been extensively described in the medical field but the effect of hyperlipidemia on dental implant osseointegration has not yet been fully elucidated. 111 Significantly more peri-implant bone loss, reduced bone formation, and lower strength in the bone-implant interface has previously been reported in mice after a 12 week high-fat diet.…”

Regulation of ABCA1 and ABCG1 gene expression in the intraabdominal adipose tissue

“…ABCA1 участвует в биогенезе ЛПВП на этапе формирования незрелых частиц пре-b-ЛПВП, в то время как ABCG1 осуществляет насыщение холестерином зрелых ЛПВП [8]. Согласно данным ряда исследований, именно транспортер ABCG1 является основным регулятором содержания холестерина в жировой ткани; он играет важную роль в адипогенезе и вовлечен в молекулярные механизмы накопления триглицеридов в адипоцитах [7][8][9][10][11]. В то же время есть данные, что транспортер ABCA1 может принимать участие в синтезе ЛПВП в жировой ткани [3].…”

Transcriptional co-regulator RIP140: An important mediator of the inflammatory response and its associated diseases

“…(ABCG1) interact with HDL to increase cholesterol efflux and promote cholesterol transportation to its lipid-depleted receptor apolipoprotein AI (apoAI), which protects against the formation of foam cells and the development of atherosclerosis (42,43). The specific mechanism remains to be elucidated; however it is apparent that RIP140 contributes to foam cell formation and atherosclerosis by regulating cholesterol homeostasis in macrophages.…”