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.
Highlights
Overweight and obesity are presently affecting close to 50% of the adult population in many Western countries and are leading to an epidemic of associated metabolic comorbidities such as type 2 diabetes and cardiovascular diseases [1]
We first determined the effects of lowfat diet (LFD) or high-fat diet (HFD) on body weight gain and body composition as well as on food intake and energy expenditure in mice that had undergone a syngeneic bone marrow transplantation (BMT) versus controls
Individual indirect calorimetry measurements using metabolic cages revealed that the decrease in body weight gain could neither be explained by decreased food intake nor by increased energy expenditure in LFD- or HFD-fed BMT-treated mice
Summary
Overweight and obesity are presently affecting close to 50% of the adult population in many Western countries and are leading to an epidemic of associated metabolic comorbidities such as type 2 diabetes and cardiovascular diseases [1]. A widely used tool to study the role of immune cells in many immune-associated disorders is experimental bone marrow transplantation (BMT) in mouse models. With this technique, host hematopoietic cells are depleted by lethal total body irradiation (TBI) and replaced by donor bone marrow cells harbouring genetic alterations in a relevant inflammatory pathway [4]. Another study showed that BMT reduced adiposity in genetically obese ob/ob mice. These mice stopped gaining weight two months after TBI, while the control mice gained weight continuously [6]
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