BMT decreases HFD-induced weight gain associated with decreased preadipocyte number and insulin secretion

PLoS One. 2017 Apr 26;12(4):e0175524. doi: 10.1371/journal.pone.0175524. eCollection 2017.

Abstract

Experimental bone marrow transplantation (BMT) in mice is commonly used to assess the role of immune cell-specific genes in various pathophysiological settings. The application of BMT in obesity research is hampered by the significant reduction in high-fat diet (HFD)-induced obesity. We set out to characterize metabolic tissues that may be affected by the BMT procedure and impair the HFD-induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal irradiation. After a recovery period of 8 weeks they were fed a low-fat diet (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as compared to HFD-fed control mice, characterized by both a reduced fat (-33%; p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure were unaffected. As compared to control mice, BMT-treated mice had a reduced mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous, gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (-46%; p<0.01) was disproportionally decreased. This was associated with reduced plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed glucose clearance in BMT-treated mice on HFD as compared to control mice. In conclusion, the reduction in HFD-induced obesity after BMT in mice is at least partly due to alterations in the adipose tissue cell pool composition as well as to a decreased pancreatic secretion of the anabolic hormone insulin. These effects should be considered when interpreting results of experimental BMT in metabolic studies.

MeSH terms

  • Adipocytes / cytology*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / immunology
  • Adipose Tissue, White / metabolism
  • Animals
  • Bone Marrow Transplantation*
  • C-Peptide / blood
  • Diet, Fat-Restricted
  • Diet, High-Fat*
  • Eating
  • Energy Metabolism
  • Fatty Acids, Nonesterified / analysis
  • Feces / chemistry
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Macrophages / cytology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / prevention & control
  • Pancreas / metabolism
  • Pancreas / pathology
  • Triglycerides / analysis
  • Weight Gain

Substances

  • C-Peptide
  • Fatty Acids, Nonesterified
  • Insulin
  • Triglycerides

Grant support

Funded by Rembrandt Institute of Cardiovascular Sciences (RICS) and Cardiovascular Research Netherlands (CVON IN-CONTROL). M.G.N was supported by an ERC Consolidator Grant (#310372). J.A.v.D. was supported by a Veni Grant of the Netherlands Organization for the Scientific Research (#91616083).