Bone marrow adipose tissue represents a unique depot surrounded by hematopoietic elements and trabecular bone. It expands during aging, and is dynamic in response to hormonal, nutritional and mechanical stimuli. The skeletal response to the increase in marrow adipocyte number and/or size is a relevant consideration, particularly since bone marrow adipose tissue is enhanced in states with low bone mass or rapid bone loss. Excess or deficient nutrient intake are powerful inducers of bone marrow adiposity in both humans and mice. We previously showed that 30% calorie restriction in mice stimulated bone marrow adiposity and drove bone loss. This led us to determine if fasting in humans also caused bone loss and expansion of marrow adipocytes. Volunteers were fasted for 10 days or given a high calorie diet for 10 days; bone marrow aspirates and skeletal quantitation was determined by uCT and MRI. Fasting induced a 10% increase in marrow fat, which was rapidly reversed by a 2 week return to a normal diet. In pathway analysis from marrow adipocytes using RNAseq, recruitment of progenitors (adipogenesis) was the major network activated, followed by the complement pathway. qRT-PCR demonstrated that adipsin, complement factor D (CFD), was one of the most up-regulated genes in the marrow adipocytes. In vitro analysis of adipocytes from the marrow of 30% CR mice revealed increased CFU-F and alkaline phosphatase staining, and enhanced adipogenic markers with increased oil-red O staining but suppressed genes associated with impaired in vitro osteogenesis. CFD mRNA was markedly increased similar to the human data. Addition of adipsin suppressed bone marrow stromal cell osteogenesis, and reduced gene expression for col1a1, osteocalcin and other bone markers. Taken together, nutrient intake regulates bone marrow adiposity and influences skeletal remodeling. We are now studying if intermittent fasting, which now is an extremely popular weight loss program, can cause bone loss and increased marrow adiposity.
21 May 2022 - 24 May 2022