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 Iron Metabolism:

Not much is known about the role of adipose tissue macrophages in tissue homeostasis.  Our recent data suggests that resident M2 macrophages may play a role in iron metabolism in fat.  These exciting findings have opened up a new area of research for our group to assess the impact of macrophage iron handling on adipose tissue homeostasis.

Publications

Featured publications

  1. 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)
  2. 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)
  3. 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)
  4. 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)
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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)
  10. 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)

Community Leaders

Contact Information

2215 Garland Ave.
702 Light Hall
Nashville, TN 37232-0615
USA
615-322-5177 (p)
615-322-8973 (f)

Alyssa Hasty
615-322-5177 (p)
615-322-8973 (f)
Email

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Animals Antigens, CD Antigens, CD3 Arteries Blotting, Western CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cholesterol, LDL Cohort Studies Diet, High-Fat Dyslipidemias Fatty Liver Gas Chromatography-Mass Spectrometry Genotype Hydrolysis Iron Monocytes Oxidative Stress Receptors, CCR5 Receptors, Scavenger