The Dynamics of Human Bone Marrow Adipose Tissue in Response to Feeding and Fasting

In collaboration with peers from other institutions, UPMC physician and researcher, Pouneh K. Fazeli, MD, conducted a study that aimed to determine the responsiveness of bone marrow adipose tissue (BMAT) to hormonal and nutrient changes. 

Research from previous studies found that while subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) levels are lower in females with anorexia nervosa when compared to normal-weight controls, BMAT levels are higher. It is unknown why BMAT would be expanded during chronic starvation while the other lipid depots are depleted. 

While the function of BMAT and its response to high-fat diets and surgical interventions (e.g., gastric bypass and sleeve gastrectomy) have previously been studied, there is limited research that focuses specifically on BMAT’s response to structured acute changes in weight and nutrient flux. This gap in knowledge prompted Dr. Fazeli and her colleagues to examine how drastic changes in nutrients affect the overall function of BMAT.

Twenty-three subjects, 10 women and 13 men, were admitted to the Translational and Clinical Research Center at the Massachusetts General Hospital for a 10-day inpatient high-calorie visit. The goal of this portion of the study was to achieve a 7% weight gain during the 10-day admission. Subjects were then discharged for approximately 2 weeks and were instructed to resume their normal diet. Following their time at home, subjects were readmitted to the TCRC for a 7- to 10-day inpatient fast in which they were not allowed any caloric intake. 

On the first and last day of the high-calorie intake and fasting visits, BMAT was measured using 1 H-magnetic resonance spectroscopy with a final assessment of change in BMAT occurring at the L4 vertebra, femoral diaphysis, and femoral metaphysis. Inflammatory mediators that have been associated with BMI, nutrient flux, and those that have been shown to be determinants of BMAT in animal models were also measured. 

Results showed that BMAT levels at the L4 vertebra, femoral diaphysis, and femoral metaphysis were significantly greater in men at the baseline analysis when compared with women. BMAT levels increased significantly during both the 10-day high-calorie feeding and 7-to 10-day fasting. This finding leads researchers to believe that BMAT may have different functions in different states of caloric excess compared with caloric deprivation. 

It should be noted that the largest change in BMAT was during the 2-week period when subjects resumed their normal diet after high-calorie feeding. During this 2-week period, there was a 17.8% decrease in L4 vertebral BMAT in women and a 20.4% decrease in L4 vertebral BMAT in men. 

Results also support the concept of region-specific variation in BMAT’s response to environmental cues, as human bone marrow adipocytes responded differently to nutrient challenges depending on their location. For example, significant BMAT accumulation location differences were observed in women versus men during fasting, with men accumulating significantly more BMAT in the L4 vertebra and women accumulating significantly more BMAT at the femoral metaphysis.

Data from marrow aspirates in this study provide insight on adipose tissue response to nutrient changes. High-calorie feeding induced a proinflammatory response with increases in TNF-α, Plexin D1, and SEMA3E gene expression in mature adipocytes at day 10, as well as a marked increase in marrow serum resistin. Additionally, results show that the timing of caloric excess or deprivation plays a major role in hormonal responses, as ghrelin levels decreased in response to both high-calorie feeding and fasting. 

Ultimately, researchers determined that high-calorie feeding, not fasting, induces an immune response in bone marrow similar to what has previously been reported in studies on peripheral adipose tissue. Data from the study supports the concept that nutrient flux rather than body weight is an important determinant of BMAT.

Read more about the results of this study here. 

Reference 

Fazeli PK, Bredella MA, Pachon-Peña G, Zhao W, Zhang X, Faje AT, Resulaj M, Polineni SP, Holmes TM, Lee H, O’Donnell EK, MacDougald OA, Horowitz MC, Rosen CJ, Klibanski A. The Dynamics of Human Bone Marrow Adipose Tissue in Response to Feeding and Fasting. JCI Insight. 2021; (12): e138636.