Profile

Research description: The growing worldwide obesity epidemic is frequently linked to hyperlipidemia, inflammation, and insulin resistance leading to increased risk of diabetes and cardiovascular disease. The long-term goal of my laboratory is to determine mechanisms by which obesity increases risk for and pathophysiological consequences of these devastating diseases. Macrophages are part of the innate immune system that infiltrate white adipose tissue in obese rodents and humans, and produce most of the inflammatory cytokines and chemokines secreted from AT. In addition, their presence has been shown to be temporally associated with the development of insulin resistance. My current research focus is to determine mechanisms by which macrophages are attracted to adipose tissue and what happens to them once they arrive.

Some of the current projects in my laboratory are: Macrophage Cell Death: The macrophages in adipose tissue are exposed to high levels of fatty acids that are released from the adipocytes either due to uncontrolled lipolysis or adipocyte cell death. We have evidence in vitro, that exposure of macrophages to saturated fatty acids induced inflammation, ER stress and apoptosis. However, it has not been determined whether ATMs undergo apoptosis. In addition, apoptotic cells are normally phagocytosed by other macrophages in a process called "efferocytosis". It is also now known whether efferocytosis can occur in AT in vivo. We are interested in whether efferocytosis occurs in AT and whether this can contribute to resolution of the inflammation. Turnover of Adipose Tissue Macrophages: We have growing evidence that even in lean adipose tissue the macrophages undergo apoptotic cell death. We would like to understand how the natural turnover of macrophages contributes to the overall numbers of cells in lean and obese adipose tissue. We hypothesize that this turnover may be impaired in obesity and contribute to the accumulation of macrophages in obese adipose tissue. Macrophage Emigration: In addition to studying mechanisms by which macrophages enter adipose tissue, we are also performing experiments to determine how their numbers decline during weight loss. This may be via increased turnover or apoptosis as described above. However, an alternative would be that they could emigrate out of adipose tissue. We have a mouse model where leukocyte emigration from tissue to nearby lymph nodes is impaired. We would like to study adipose tissue macrophage emigration in this model.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice. Orr JS, Kennedy AJ, Hill AA, Anderson-Baucum EK, Hubler MJ, Hasty AH (2016) Physiol Rep 4(18)
    › Primary publication · 27655794 (PubMed) · PMC5037919 (PubMed Central)
  2. Fat-water MRI of a diet-induced obesity mouse model at 15.2T. Ong HH, Webb CD, Gruen ML, Hasty AH, Gore JC, Welch EB (2016) J Med Imaging (Bellingham) 3(2): 026002
    › Primary publication · 27226976 (PubMed) · PMC4877437 (PubMed Central)
  3. Activation of NF-κB drives the enhanced survival of adipose tissue macrophages in an obesogenic environment. Hill AA, Anderson-Baucum EK, Kennedy AJ, Webb CD, Yull FE, Hasty AH (2015) Mol Metab 4(10): 665-77
    › Primary publication · 26779432 (PubMed) · PMC4588436 (PubMed Central)
  4. Macrophages are essential for CTGF-mediated adult β-cell proliferation after injury. Riley KG, Pasek RC, Maulis MF, Dunn JC, Bolus WR, Kendall PL, Hasty AH, Gannon M (2015) Mol Metab 4(8): 584-91
    › Primary publication · 26266091 (PubMed) · PMC4529497 (PubMed Central)
  5. Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity. Wainright KS, Fleming NJ, Rowles JL, Welly RJ, Zidon TM, Park YM, Gaines TL, Scroggins RJ, Anderson-Baucum EK, Hasty AH, Vieira-Potter VJ, Padilla J (2015) Am J Physiol Regul Integr Comp Physiol 309(5): R594-602
    › Primary publication · 26180183 (PubMed) · PMC4591377 (PubMed Central)
  6. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue. Bolus WR, Gutierrez DA, Kennedy AJ, Anderson-Baucum EK, Hasty AH (2015) J Leukoc Biol 98(4): 467-77
    › Primary publication · 25934927 (PubMed) · PMC4763864 (PubMed Central)
  7. Iron homeostasis: a new job for macrophages in adipose tissue? Hubler MJ, Peterson KR, Hasty AH (2015) Trends Endocrinol Metab 26(2): 101-9
    › Primary publication · 25600948 (PubMed) · PMC4315734 (PubMed Central)
  8. A decade of progress in adipose tissue macrophage biology. Hill AA, Reid Bolus W, Hasty AH (2014) Immunol Rev 262(1): 134-52
    › Primary publication · 25319332 (PubMed) · PMC4203421 (PubMed Central)
  9. Striatal dopamine homeostasis is altered in mice following Roux-en-Y gastric bypass surgery. Reddy IA, Wasserman DH, Ayala JE, Hasty AH, Abumrad NN, Galli A (2014) ACS Chem Neurosci 5(10): 943-51
    › Primary publication · 25068716 (PubMed) · PMC4324416 (PubMed Central)
  10. Regulation of S100B in white adipose tissue by obesity in mice. Buckman LB, Anderson-Baucum EK, Hasty AH, Ellacott KLj (2014) Adipocyte 3(3): 215-20
    › Primary publication · 25068089 (PubMed) · PMC4110099 (PubMed Central)
  11. A possible secondary immune response in adipose tissue during weight cycling: The ups and downs of yo-yo dieting. Anderson-Baucum EK, Major AS, Hasty AH (2014) Adipocyte 3(2): 141-5
    › Primary publication · 24719788 (PubMed) · PMC3979879 (PubMed Central)
  12. What have we really learned about macrophage recruitment to adipose tissue? Hasty AH, Gutierrez DA (2014) Endocrinology 155(1): 12-4
    › Primary publication · 24364586 (PubMed) · PMC3868801 (PubMed Central)
  13. Liver X receptor α-dependent iron handling in M2 macrophages: The missing link between cholesterol and intraplaque hemorrhage? Hasty AH, Yvan-Charvet L (2013) Circ Res 113(11): 1182-5
    › Citation · 24201110 (PubMed)
  14. Obesity alters adipose tissue macrophage iron content and tissue iron distribution. Orr JS, Kennedy A, Anderson-Baucum EK, Webb CD, Fordahl SC, Erikson KM, Zhang Y, Etzerodt A, Moestrup SK, Hasty AH (2014) Diabetes 63(2): 421-32
    › Primary publication · 24130337 (PubMed) · PMC3900546 (PubMed Central)
  15. Loss of CCR5 results in glucose intolerance in diet-induced obese mice. Kennedy A, Webb CD, Hill AA, Gruen ML, Jackson LG, Hasty AH (2013) Am J Physiol Endocrinol Metab 305(7): E897-906
    › Primary publication · 23941876 (PubMed) · PMC3798705 (PubMed Central)
  16. Weight cycling increases T-cell accumulation in adipose tissue and impairs systemic glucose tolerance. Anderson EK, Gutierrez DA, Kennedy A, Hasty AH (2013) Diabetes 62(9): 3180-8
    › Primary publication · 23733197 (PubMed) · PMC3749340 (PubMed Central)
  17. Isolation of adipose tissue immune cells. Orr JS, Kennedy AJ, Hasty AH (2013) J Vis Exp (75): e50707
    › Primary publication · 23728515 (PubMed) · PMC3718226 (PubMed Central)
  18. Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages. Orr JS, Puglisi MJ, Ellacott KL, Lumeng CN, Wasserman DH, Hasty AH (2012) Diabetes 61(11): 2718-27
    › Primary publication · 22751700 (PubMed) · PMC3478520 (PubMed Central)
  19. Stearic acid accumulation in macrophages induces toll-like receptor 4/2-independent inflammation leading to endoplasmic reticulum stress-mediated apoptosis. Anderson EK, Hill AA, Hasty AH (2012) Arterioscler Thromb Vasc Biol 32(7): 1687-95
    › Primary publication · 22556332 (PubMed) · PMC3385654 (PubMed Central)
  20. Impact of macrophage inflammatory protein-1α deficiency on atherosclerotic lesion formation, hepatic steatosis, and adipose tissue expansion. Kennedy A, Gruen ML, Gutierrez DA, Surmi BK, Orr JS, Webb CD, Hasty AH (2012) PLoS One 7(2): e31508
    › Primary publication · 22359597 (PubMed) · PMC3281060 (PubMed Central)
  21. Haematopoietic leptin receptor deficiency does not affect macrophage accumulation in adipose tissue or systemic insulin sensitivity. Gutierrez DA, Hasty AH (2012) J Endocrinol 212(3): 343-51
    › Primary publication · 22194312 (PubMed) · PMC3381898 (PubMed Central)
  22. Aberrant accumulation of undifferentiated myeloid cells in the adipose tissue of CCR2-deficient mice delays improvements in insulin sensitivity. Gutierrez DA, Kennedy A, Orr JS, Anderson EK, Webb CD, Gerrald WK, Hasty AH (2011) Diabetes 60(11): 2820-9
    › Primary publication · 21926275 (PubMed) · PMC3198070 (PubMed Central)
  23. The role of adipose tissue in mediating the beneficial effects of dietary fish oil. Puglisi MJ, Hasty AH, Saraswathi V (2011) J Nutr Biochem 22(2): 101-8
    › Primary publication · 21145721 (PubMed) · PMC3038466 (PubMed Central)
  24. Absence of macrophage inflammatory protein-1{alpha} does not impact macrophage accumulation in adipose tissue of diet-induced obese mice. Surmi BK, Webb CD, Ristau AC, Hasty AH (2010) Am J Physiol Endocrinol Metab 299(3): E437-45
    › Primary publication · 20551286 (PubMed) · PMC2944285 (PubMed Central)
  25. Adipose tissue recruitment of leukocytes. Anderson EK, Gutierrez DA, Hasty AH (2010) Curr Opin Lipidol 21(3): 172-7
    › Primary publication · 20410821 (PubMed) · PMC3381420 (PubMed Central)
  26. Mouse models of the metabolic syndrome. Kennedy AJ, Ellacott KL, King VL, Hasty AH (2010) Dis Model Mech 3(3-4): 156-66
    › Primary publication · 20212084 (PubMed) · PMC2869491 (PubMed Central)
  27. The role of chemokines in recruitment of immune cells to the artery wall and adipose tissue. Surmi BK, Hasty AH (2010) Vascul Pharmacol 52(1-2): 27-36
    › Primary publication · 20026286 (PubMed) · PMC2823842 (PubMed Central)
  28. Dietary fish oil exerts hypolipidemic effects in lean and insulin sensitizing effects in obese LDLR-/- mice. Saraswathi V, Morrow JD, Hasty AH (2009) J Nutr 139(12): 2380-6
    › Primary publication · 19864403 (PubMed) · PMC2777481 (PubMed Central)
  29. Inhibition of long-chain acyl coenzyme A synthetases during fatty acid loading induces lipotoxicity in macrophages. Saraswathi V, Hasty AH (2009) Arterioscler Thromb Vasc Biol 29(11): 1937-43
    › Primary publication · 19679826 (PubMed) · PMC2766024 (PubMed Central)
  30. Impact of increased adipose tissue mass on inflammation, insulin resistance, and dyslipidemia. Gutierrez DA, Puglisi MJ, Hasty AH (2009) Curr Diab Rep 9(1): 26-32
    › Primary publication · 19192421 (PubMed) · PMC2735041 (PubMed Central)
  31. Impact of macrophage toll-like receptor 4 deficiency on macrophage infiltration into adipose tissue and the artery wall in mice. Coenen KR, Gruen ML, Lee-Young RS, Puglisi MJ, Wasserman DH, Hasty AH (2009) Diabetologia 52(2): 318-28
    › Primary publication · 19052722 (PubMed) · PMC2615827 (PubMed Central)
  32. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Surmi BK, Hasty AH (2008) Future Lipidol 3(5): 545-556
    › Primary publication · 18978945 (PubMed) · PMC2575346 (PubMed Central)
  33. Atherosclerotic lesion formation and triglyceride storage in obese apolipoprotein AI-deficient mice. Plummer MR, Hasty AH (2008) J Nutr Biochem 19(10): 664-73
    › Primary publication · 18280133 (PubMed)
  34. The role of macrophage leptin receptor in aortic root lesion formation. Surmi BK, Atkinson RD, Gruen ML, Coenen KR, Hasty AH (2008) Am J Physiol Endocrinol Metab 294(3): E488-95
    › Primary publication · 18182468 (PubMed)
  35. Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice. Atkinson RD, Coenen KR, Plummer MR, Gruen ML, Hasty AH (2008) Am J Physiol Endocrinol Metab 294(2): E284-90
    › Primary publication · 18029445 (PubMed)
  36. Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice. Nuotio-Antar AM, Hachey DL, Hasty AH (2007) Am J Physiol Endocrinol Metab 293(6): E1517-28
    › Primary publication · 17878220 (PubMed)
  37. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. Gruen ML, Hao M, Piston DW, Hasty AH (2007) Am J Physiol Cell Physiol 293(5): C1481-8
    › Primary publication · 17728393 (PubMed)
  38. Fish oil increases cholesterol storage in white adipose tissue with concomitant decreases in inflammation, hepatic steatosis, and atherosclerosis in mice. Saraswathi V, Gao L, Morrow JD, Chait A, Niswender KD, Hasty AH (2007) J Nutr 137(7): 1776-82
    › Primary publication · 17585030 (PubMed)
  39. Obesity potentiates development of fatty liver and insulin resistance, but not atherosclerosis, in high-fat diet-fed agouti LDLR-deficient mice. Coenen KR, Hasty AH (2007) Am J Physiol Endocrinol Metab 293(2): E492-9
    › Primary publication · 17566116 (PubMed)
  40. Obesity causes very low density lipoprotein clearance defects in low-density lipoprotein receptor-deficient mice. Coenen KR, Gruen ML, Hasty AH (2007) J Nutr Biochem 18(11): 727-35
    › Primary publication · 17418556 (PubMed)
  41. Diet-induced increases in adiposity, but not plasma lipids, promote macrophage infiltration into white adipose tissue. Coenen KR, Gruen ML, Chait A, Hasty AH (2007) Diabetes 56(3): 564-73
    › Primary publication · 17327423 (PubMed)
  42. Effects of vitamin E on oxidative stress and atherosclerosis in an obese hyperlipidemic mouse model. Hasty AH, Gruen ML, Terry ES, Surmi BK, Atkinson RD, Gao L, Morrow JD (2007) J Nutr Biochem 18(2): 127-33
    › Primary publication · 16781857 (PubMed)
  43. The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritoneal macrophages. Saraswathi V, Hasty AH (2006) J Lipid Res 47(7): 1406-15
    › Primary publication · 16639077 (PubMed)
  44. Plasma insulin levels predict atherosclerotic lesion burden in obese hyperlipidemic mice. Gruen ML, Saraswathi V, Nuotio-Antar AM, Plummer MR, Coenen KR, Hasty AH (2006) Atherosclerosis 186(1): 54-64
    › Primary publication · 16102772 (PubMed)
  45. Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. Gruen ML, Plummer MR, Zhang W, Posey KA, Linton MF, Fazio S, Hasty AH (2005) J Lipid Res 46(9): 2007-14
    › Primary publication · 15995171 (PubMed)
  46. The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I. Hasty AH, Plummer MR, Weisgraber KH, Linton MF, Fazio S, Swift LL (2005) J Lipid Res 46(7): 1433-9
    › Primary publication · 15805547 (PubMed)
  47. Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor. Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M, Yoshikawa T, Okazaki H, Ohashi K, Harada K, Matsuzaka T, Sone H, Gotoda T, Nagai R, Ishibashi S, Yamada N (2001) J Biol Chem 276(40): 37402-8
    › Primary publication · 11445560 (PubMed)
  48. Sterol regulatory element-binding protein-1 is regulated by glucose at the transcriptional level. Hasty AH, Shimano H, Yahagi N, Amemiya-Kudo M, Perrey S, Yoshikawa T, Osuga J, Okazaki H, Tamura Y, Iizuka Y, Shionoiri F, Ohashi K, Harada K, Gotoda T, Nagai R, Ishibashi S, Yamada N (2000) J Biol Chem 275(40): 31069-77
    › Primary publication · 10913129 (PubMed)
  49. Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance. Hasty AH, Linton MF, Swift LL, Fazio S (1999) J Lipid Res 40(8): 1529-38
    › Primary publication · 10428991 (PubMed)
  50. Retroviral gene therapy in ApoE-deficient mice: ApoE expression in the artery wall reduces early foam cell lesion formation. Hasty AH, Linton MF, Brandt SJ, Babaev VR, Gleaves LA, Fazio S (1999) Circulation 99(19): 2571-6
    › Primary publication · 10330390 (PubMed)