Skeletal integration of energy homeostasis: Translational implications

Lecka‐Czernik, Beata; Rosen, Clifford J.

doi:10.1016/j.bone.2015.07.026

Cited by 13 publications

(3 citation statements)

References 99 publications

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“…Adipocytes are mature, lipid‐laden cells that are found in individual, discrete depots distributed throughout the body; however, this is by no means always the case, as adipocytes can also be found in nonadipose tissue, such as bone, liver, skin, muscle, and heart . In each adipose tissue depot, many other different cell types comingle with adipocytes, including cells from the immune system, vascular system, and nervous system (Fig.…”

Section: Cellular Heterogeneity Of Adipose Tissuementioning

confidence: 99%

Deciphering adipose tissue heterogeneity

Lynes

Tseng

2017

Annals of the New York Academy of Sciences

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Obesity is an excess accumulation of adipose tissue mass, and, together with its sequelae, in particular type II diabetes and metabolic syndrome, obesity presents a major health crisis. Although obesity is simply caused by increased adipose mass, the heterogeneity of adipose tissue in humans means that the response to increased energy balance is highly complex. Individual subjects with similar phenotypes may respond very differently to the same treatments; therefore, obesity may benefit from a personalized precision medicine approach. The variability in the development of obesity is indeed driven by differences in sex, genetics, and environment, but also by the various types of adipose tissue as well as the different cell types that compose it. By describing the distinct cell populations that reside in different fat depots, we can interpret the complex effect of these various players in the maintenance of wholebody energy homeostasis. To further understand adipose tissue, adipogenic differentiation and the transcriptional program of lipid accumulation must be investigated. As the cell-and depot-specific functions are described, they can be placed in the context of energy excess to understand how the heterogeneity of adipose tissue shapes individual metabolic status and condition.

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Section: Cellular Heterogeneity Of Adipose Tissuementioning

confidence: 99%

Deciphering adipose tissue heterogeneity

Lynes

Tseng

2017

Annals of the New York Academy of Sciences

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“…The skeleton is classically understood to be a structural organ allowing body movements, organ protection, and a site for hematopoiesis and calcium storage. However, recent advances in mouse models support a function of this organ in additional physiological processes, including energy metabolism ( Rosen, 2016 ; Wei et al, 2015 ; Sato et al, 2013 ), behavior ( Khrimian et al, 2017 ), reproduction ( Oury et al, 2013 ; Karsenty and Oury, 2014 ), and as an endocrine organ ( Fukumoto and Martin, 2009 ; DiGirolamo et al, 2012 ). As such, the skeleton can be expected to be both the target and the source of endocrine, paracrine, and neuronal signals that integrate its functions with other tissues and organs.…”

Section: Introductionmentioning

confidence: 99%

Cortical bone is an extraneuronal site of norepinephrine uptake in adult mice

Zhu

Elefteriou

2018

Bone Reports

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The sympathetic nervous system is a major efferent pathway through which the central nervous system controls the function of peripheral organs. Genetic and pharmacologic evidence in mice indicated that stimulation of the β2 adrenergic receptor (β2AR) in osteoblasts promotes bone loss, leading to the paradigm that high sympathetic nervous activity is deleterious to bone mass. However, considerably less data exist to understand the putative impact of endogenous norepinephrine (NE), released by sympathetic nerves, on bone homeostasis. In this study, we investigated the in vivo expression and activity of the norepinephrine transporter (NET), a membrane pump known to actively uptake NE from the extracellular space in presynaptic neurons. Consistent with previously published in vitro data showing NET uptake activity in differentiated osteoblasts, we were able to detect active NET-specific NE uptake in the mouse cortical bone compartment in vivo. This uptake was the highest in young mice and accordingly with an age-related reduction in NET uptake, NE bone content increased whereas Net RNA and protein expression decreased with age. Histologically, NET expression in adult mouse bones was detected in osteocytes via immunofluorescence. Lastly, taking advantage of tissue-specific fluorescent reporter mice, we used CLARITY imaging and light sheet microscopy to visualize the 3D distribution of sympathetic fibers in whole mount preparations of bone tissues. These analyses allowed us to detect tyrosine hydroxylase (TH)-positive sympathetic nerve fibers penetrating the cortical bone, where NET+ osteocytes reside. Together, these in vitro results support the existence of an age-dependent extraneuronal and osteocytic function of NET with potential to buffer the bone catabolic action of endogenous NE released by sympathetic nerves in vivo.

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“…On the other hand, caloric restriction increases MAT volume predominantly in proximal but not in distal location ( 7 ). The differences between these two MAT depots may be attributed to the heterogeneity of marrow adipocytes with respect to their origin and function ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Marrow Adipose Tissue: Skeletal Location, Sexual Dimorphism, and Response to Sex Steroid Deficiency

et al. 2017

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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.

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Skeletal integration of energy homeostasis: Translational implications

Cited by 13 publications

References 99 publications

Deciphering adipose tissue heterogeneity

Deciphering adipose tissue heterogeneity

Cortical bone is an extraneuronal site of norepinephrine uptake in adult mice

Marrow Adipose Tissue: Skeletal Location, Sexual Dimorphism, and Response to Sex Steroid Deficiency

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