# FAT TALKS TO BONE

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

Abstract
Obesity and osteoporosis are endemic in our society yet their relationship is perplexing. While obesity has
long been considered beneficial for skeletal health, recent studies suggest bone mass is diminished in a
substantial subset of obese individuals. Thus, despite its demographic importance, the influence of fat on bone
remains enigmatic. Although controversial, studies of the effect of fat-produced molecules, such as leptin and
adiponectin, indicate these selected adipokines impact bone. Adipose tissue is, however, a complex organ and
there is little mechanistic insight as to how fat, per se, and which variety of fat, regulates the skeleton. Such
information is clinically relevant as individuals with a predominance of visceral fat are osteopenic whereas
subcutaneous and brown fat may positively influence bone mass.
 Determination of how fat, in its various forms, targets bone cells will provide the framework for
ameliorating the skeletal complications of obesity. Resolution of this issue, in patients, is limited, however, by
the absence of an animal model in which manipulation of fat abundance eventuates in a robust skeletal
phenotype. To this end, we generated mice completely lacking visceral, subcutaneous and brown fat. Despite
the hypogonadal state of these "fat free" (FF) mice, trabecular bone volume is strikingly increased (400-500%)
due to enhanced osteoblast activity. Unexpectedly in face of its marked increase in bone mass,
osteoclastogenesis in FF mice is also markedly enhanced. This observation raises the possibility that visceral
fat diminishes bone mass by arresting osteoclast-induced remodeling.
 Our observations establish that, by mechanisms to be determined, fat signals to bone and decreased
adiposity may greatly increase bone mass, challenging the concept that obesity generally improves skeletal
health. Most importantly, the skeletal phenotype of FF mice is completely rescued by adipocyte precursor
transplantation. This transplantation-mediated normalization of FF bone provides the opportunity to directly
explore the impact of deleting various adipocyte products on bone accrual and how visceral, subcutaneous
and/or brown adipose tissue targets the skeleton. Hence, we hypothesize that fat diminishes bone accrual in
an osteoblast- and osteoclast-dependent manner.

## Key facts

- **NIH application ID:** 9978044
- **Project number:** 5R01DK111389-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Steven L Teitelbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-07-11 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978044

## Citation

> US National Institutes of Health, RePORTER application 9978044, FAT TALKS TO BONE (5R01DK111389-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978044. Licensed CC0.

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