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What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health.

ABSTRACT: Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot.

SUBMITTER: Scheller EL

PROVIDER: S-EPMC4049420 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health.

Scheller Erica L EL Rosen Clifford J CJ

Annals of the New York Academy of Sciences 20140320

Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target f ...[more]

PMID: 24650218

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Project description:Marrow adipose tissue (MAT) is unique with respect to origin, metabolism, and function. MAT is characterized with high heterogeneity which correlates with skeletal location and bone metabolism. This fat depot is also highly sensitive to various hormonal, environmental, and pharmacologic cues to which it responds with changes in volume and/or metabolic phenotype. We have demonstrated previously that MAT has characteristics of both white (WAT) and brown (BAT)-like or beige adipose tissue, and that beige phenotype is attenuated with aging and in diabetes. Here, we extended our analysis by comparing MAT phenotype in different locations within a tibia bone of mature C57BL/6 mice and with respect to the presence of sex steroids in males and females. We report that MAT juxtaposed to trabecular bone of proximal tibia (pMAT) is characterized by elevated expression of beige fat markers including Ucp1, HoxC9, Prdm16, Tbx1, and Dio2, when compared with MAT located in distal tibia (dMAT). There is also a difference in tissue organization with adipocytes in proximal tibia being dispersed between trabeculae, while adipocytes in distal tibia being densely packed. Higher trabecular bone mass (BV/TV) in males correlates with lower pMAT volume and higher expression of beige markers in the same location, when compared with females. However, there is no sexual divergence in the volume and transcriptional profile of dMAT. A removal of ovaries in females resulted in decreased cortical bone mass and increased volume of both pMAT and dMAT, as well as volume of gonadal WAT (gWAT). Increase in pMAT volume was associated with marked increase in Fabp4 and Adiponectin expression and relative decrease in beige fat gene markers. A removal of testes in males resulted in cortical and trabecular bone loss and the tendency to increased volume of both pMAT and dMAT, despite a loss of gWAT. Orchiectomy did not affect the expression of white and beige adipocyte gene markers. In conclusion, expression profile of beige adipocyte gene markers correlates with skeletal location of active bone remodeling and higher BV/TV, however bone loss resulted from sex steroid deficiency is not proportional to MAT expansion at the same skeletal location.

Project description:Irisin is an exercise-induced hormone that regulates lipid metabolism. The present study investigates whether the anti-obesity effect of the natural flavonoid pentamethylquercetin (PMQ) is related to irisin secretion from skeletal muscle in whole animals and cultured cells. Obese mice induced by monosodium glutamate were administered oral PMQ to determine blood irisin level and in vivo parameters of lipid metabolism, and cultured mouse C2C12 myoblasts and 3T3-L1 preadipocytes were employed to investigate the related molecular identities. PMQ increased circulating irisin and decreased bodyweight, insulin, and lipid levels accompanied with increasing brown-like adipocyte formation in obese mice. The brown adipocyte marker uncoupling protein 1 (UCP-1) and other brown-like adipocyte-specific genes and/or markers were increased in mouse white fat tissue, while PMQ treatment reversed the above changes. PMQ also dose-dependently increased the reduced levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and fibronectin type III domain-containing 5 (FNDC5) signal molecules in obese mice. Interestingly, the irisin level was increased in the culture medium of C2C12 cells treated with PMQ, and the conditioned medium stimulated the brown-like transition of 3T3-L1 preadipocytes with the increased expression of PGC-1α, FNDC5, UCP-1, and other brown-like adipocyte-specific genes. The effects of conditioned culture medium were abolished in C2C12 cells with silenced PGC-1α. On the other hand, PMQ-induced upregulation of PGC-1α and FNDC5 expression was reduced by AMPK inhibitor Compound C in C2C12 cells. Our results demonstrate the novel information that PMQ-induced irisin secretion from skeletal muscle involves the improvement of metabolic dysfunction in obese mice via activating the AMPK/PGC-1α/FNDC5 signal pathway, suggesting that PMQ modulates skeletal muscle-adipose tissue crosstalk and may be a promising drug candidate for treating obesity and obesity-related metabolic diseases.

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Project description:Key pointsMuscle infiltration with adipose tissue (IMAT) is common and associated with loss of skeletal muscle strength and physical function across a diverse set of pathologies. Whether the association between IMAT and muscle weakness is causative or simply correlative remains an open question that needs to be addressed to effectively guide muscle strengthening interventions in people with increased IMAT. In the present studies, we demonstrate that IMAT deposition causes decreased muscle strength using mouse models. These findings indicate IMAT is a novel therapeutic target for muscle dysfunction.AbstractIntramuscular adipose tissue (IMAT) is associated with deficits in strength and physical function across a wide array of conditions, from injury to ageing to metabolic disease. Due to the diverse aetiologies of the primary disorders involving IMAT and the strength of the associations, it has long been proposed that IMAT directly contributes to this muscle dysfunction. However, infiltration of IMAT and reduced strength could both be driven by muscle disuse, injury and systemic disease, making IMAT simply an 'innocent bystander.' Here, we utilize novel mouse models to evaluate the direct effect of IMAT on muscle contraction. First, we utilize intramuscular glycerol injection in wild-type mice to evaluate IMAT in the absence of systemic disease. In this model we find that, in isolation from the neuromuscular and circulatory systems, there remains a muscle-intrinsic association between increased IMAT volume and decreased contractile tension (r2 > 0.5, P < 0.01) that cannot be explained by reduction in contractile material. Second, we utilize a lipodystrophic mouse model which cannot generate adipocytes to 'rescue' the deficits. We demonstrate that without IMAT infiltration, glycerol treatment does not reduce contractile force (P > 0.8). Taken together, this indicates that IMAT is not an inert feature of muscle pathology but rather has a direct impact on muscle contraction. This finding suggests that novel strategies targeting IMAT may improve muscle strength and function in a number of populations.

Dataset Information

What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health.

Publications

What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health.

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