Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
- University of Michigan-Ann Arbor, United States
- Maine Medical Center Research Institute, United States
Abstract
To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, Pnpla2 gene). BMAd-Pnpla2-/- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 deficiency compounds the effects of caloric restriction on loss of trabecular bone in male mice, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.
Data availability
The accession number for the BMAT bulk RNA seq data reported in this paper is GEO: GSE183784.
Article and author information
Author details
Kanakadurga Singer
Funding
National Institutes of Health (R01 DK62876)
- Ormond MacDougald
National Institutes of Health (T32 DK071212)
- Kenneth T Lewis
National Institutes of Health (F32 DK122654)
- Kenneth T Lewis
National Institutes of Health (T32 DK101357)
- Rebecca L Schill
National Institutes of Health (F32 DK123887)
- Rebecca L Schill
National Institutes of Health (R01AR066028)
- Kurt D Hankenson
National Institutes of Health (R24DK092759)
- Clifford J Rosen
American Diabetes Association (1-18-PDF-087)
- Ziru Li
American Heart Association (20-PAF00361)
- Emily Bowers
National Institutes of Health (R24 DK092759)
- Ormond MacDougald
National Institutes of Health (R01 DK126230)
- Ormond MacDougald
National Institutes of Health (R01 AG069795)
- Ormond MacDougald
National Institutes of Health (T32 GM835326)
- Steven M Romanelli
National Institutes of Health (F31 DK12272301)
- Steven M Romanelli
National Institutes of Health (T32 HD007505)
- Devika P Bagchi
National Institutes of Health (T32 GM007863)
- Devika P Bagchi
National Institutes of Health (R01DK115583)
- Kanakadurga Singer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the University of Michigan Committee on the Use and Care of Animals with the protocol number as PRO00009687.
Copyright
© 2022, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,904
- views
-
- 1,033
- downloads
-
- 56
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
eLife 11:e78496.
https://doi.org/10.7554/eLife.78496
Further reading
-
- Cell Biology
- Developmental Biology
In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.
-
- Cell Biology
Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging to follow the fate of ingested bacteria, we demonstrate that while commensal Lactiplantibacillus plantarum freely circulate within the intestinal lumen, pathogenic strains such as Erwinia carotovora or Bacillus thuringiensis, are blocked in the anterior midgut where they are rapidly eliminated by antimicrobial peptides. This sequestration of pathogenic bacteria in the anterior midgut requires the Duox enzyme in enterocytes, and both TrpA1 and Dh31 in enteroendocrine cells. Supplementing larval food with hCGRP, the human homolog of Dh31, is sufficient to block the bacteria, suggesting the existence of a conserved mechanism. While the immune deficiency (IMD) pathway is essential for eliminating the trapped bacteria, it is dispensable for the blockage. Genetic manipulations impairing bacterial compartmentalization result in abnormal colonization of posterior midgut regions by pathogenic bacteria. Despite a functional IMD pathway, this ectopic colonization leads to bacterial proliferation and larval death, demonstrating the critical role of bacteria anterior sequestration in larval defense. Our study reveals a temporal orchestration during which pathogenic bacteria, but not innocuous, are confined in the anterior part of the midgut in which they are eliminated in an IMD-pathway-dependent manner.
