scholarly journals Bone marrow fat: friend or foe in people with diabetes mellitus?

2020 ◽  
Vol 134 (8) ◽  
pp. 1031-1048 ◽  
Author(s):  
Marianna Santopaolo ◽  
Yue Gu ◽  
Gaia Spinetti ◽  
Paolo Madeddu
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Current Knowledge ◽  
Cardiovascular Complications ◽  
Overweight And Obesity ◽  
Whole Body ◽  
Marrow Fat ◽  
Global Trends ◽  
New Treatments ◽  
And Function

Abstract Global trends in the prevalence of overweight and obesity put the adipocyte in the focus of huge medical interest. This review highlights a new topic in adipose tissue biology, namely the emerging pathogenic role of fat accumulation in bone marrow (BM). Specifically, we summarize current knowledge about the origin and function of BM adipose tissue (BMAT), provide evidence for the association of excess BMAT with diabetes and related cardiovascular complications, and discuss potential therapeutic approaches to correct BMAT dysfunction. There is still a significant uncertainty about the origins and function of BMAT, although several subpopulations of stromal cells have been suggested to have an adipogenic propensity. BM adipocytes are higly plastic and have a distinctive capacity to secrete adipokines that exert local and endocrine functions. BM adiposity is abundant in elderly people and has therefore been interpreted as a component of the whole-body ageing process. BM senescence and BMAT accumulation has been also reported in patients and animal models with Type 2 diabetes, being more pronounced in those with ischaemic complications. Understanding the mechanisms responsible for excess and altered function of BMAT could lead to new treatments able to preserve whole-body homeostasis.

scholarly journals The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

2018 ◽  
Vol 237 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Patricia K Russell ◽  
Salvatore Mangiafico ◽  
Barbara C Fam ◽  
Michele V Clarke ◽  
Evelyn S Marin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Androgen Receptor ◽  
Progenitor Cells ◽  
Fat Mass ◽  
Elevated Serum ◽  
Gene Replacement ◽  
Whole Body ◽  
Clinical Aspects ◽  
Mesenchymal Progenitor Cells

It is well established that testosterone negatively regulates fat mass in humans and mice; however, the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass and decreased bone and muscle mass. We now show that replacement of the Ar gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50–80% lower than wild-type (WT) and 75–90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and visceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene Replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat. In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

scholarly journals Bone marrow adipose tissue does not express UCP1 during development or adrenergic-induced remodeling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Clarissa S. Craft ◽  
Hero Robles ◽  
Madelyn R. Lorenz ◽  
Eric D. Hilker ◽  
Kristann L. Magee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Enrichment Analysis ◽  
Whole Body ◽  
Mineral Density ◽  
Bone Marrow Adipose Tissue ◽  
Marrow Adipose Tissue ◽  
Reporter Mice ◽  
Brown Adipose

AbstractAdipocytes within the skeleton are collectively termed bone marrow adipose tissue (BMAT). BMAT contributes to peripheral and local metabolism, however, its capacity for cell-autonomous expression of uncoupling protein 1 (UCP1), a biomarker of beige and brown adipogenesis, remains unclear. To overcome this, Ucp1-Cre was used to drive diphtheria toxin expression in cells expressing UCP1 (Ucp1Cre+/DTA+). Despite loss of brown adipose tissue, BMAT volume was not reduced in Ucp1Cre+/DTA+ mice. Comparably, in mTmG reporter mice (Ucp1Cre+/mTmG+), Ucp1-Cre expression was absent from BMAT in young (3-weeks) and mature (16-weeks) male and female mice. Further, β3-agonist stimulation failed to induce Ucp1-Cre expression in BMAT. This demonstrates that BMAT adipocytes are not UCP1-expressing beige/brown adipocytes. Thus, to identify novel and emerging roles for BMAT adipocytes in skeletal and whole-body homeostasis, we performed gene enrichment analysis of microarray data from adipose tissues of adult rabbits. Pathway analysis revealed genetic evidence for differences in BMAT including insulin resistance, decreased fatty acid metabolism, and enhanced contributions to local processes including bone mineral density through candidate genes such as osteopontin. In sum, this supports a paradigm by which BMAT adipocytes are a unique subpopulation that is specialized to support cells within the skeletal and hematopoietic niche.

scholarly journals Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 358 ◽  
Author(s):  
Diana C. Muñoz-Lasso ◽  
Carlos Romá-Mateo ◽  
Federico V. Pallardó ◽  
Pilar Gonzalez-Cabo
Keyword(s):  
Neurological Disorders ◽  
Actin Filaments ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Three Dimensional ◽  
Cytoskeletal Proteins ◽  
Dimensional Lattice ◽  
New Treatments ◽  
And Function

Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.

scholarly journals Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice

2016 ◽  
Vol 229 (3) ◽  
pp. 295-306 ◽  
Author(s):  
M J Devlin ◽  
D J Brooks ◽  
C Conlon ◽  
M van Vliet ◽  
L Louis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Body Mass ◽  
Body Fat ◽  
Whole Body ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Marrow Fat ◽  
Bone Marrow Fat ◽  
Skeletal Acquisition

Starvation induces low bone mass and high bone marrow adiposity in humans, but the underlying mechanisms are poorly understood. The adipokine leptin falls in starvation, suggesting that hypoleptinemia may be a link between negative energy balance, bone marrow fat accumulation, and impaired skeletal acquisition. In that case, treating mice with leptin during caloric restriction (CR) should reduce marrow adipose tissue (MAT) and improve bone mass. To test this hypothesis, female C57Bl/6J mice were fed a 30% CR or normal (N) diet from 5 to 10 weeks of age, with daily injections of vehicle (VEH), 1mg/kg leptin (LEP1), or 2mg/kg leptin (LEP2) (N=6–8/group). Outcomes included body mass, body fat percentage, and whole-body bone mineral density (BMD) via peripheral dual-energy X-ray absorptiometry, cortical and trabecular microarchitecture via microcomputed tomography (μCT), and MAT volume via μCT of osmium tetroxide-stained bones. Overall, CR mice had lower body mass, body fat percentage, BMD, and cortical bone area fraction, but more connected trabeculae, vs N mice (P<0.05 for all). Most significantly, although MAT was elevated in CR vs N overall, leptin treatment blunted MAT formation in CR mice by 50% vs VEH (P<0.05 for both leptin doses). CR LEP2 mice weighed less vs CR VEH mice at 9–10 weeks of age (P<0.05), but leptin treatment did not affect body fat percentage, BMD, or bone microarchitecture within either diet. These data demonstrate that once daily leptin bolus during CR inhibits bone marrow adipose expansion without affecting bone mass acquisition, suggesting that leptin has distinct effects on starvation-induced bone marrow fat formation and skeletal acquisition.

scholarly journals Deciphering Adipose Tissue Extracellular Vesicles Protein Cargo and Its Role in Obesity

2020 ◽  
Vol 21 (24) ◽  
pp. 9366
Author(s):  
Tamara Camino ◽  
Nerea Lago-Baameiro ◽  
Aurelio Martis-Sueiro ◽  
Iván Couto ◽  
Francisco Santos ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Local Level ◽  
Functional Roles ◽  
Intracellular Proteins ◽  
Key Players ◽  
Membrane Antigens ◽  
And Function

The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue (AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action.

scholarly journals Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes

Bone ◽  
2012 ◽  
Vol 50 (2) ◽  
pp. 546-552 ◽  
Author(s):  
A. Krings ◽  
S. Rahman ◽  
S. Huang ◽  
Y. Lu ◽  
P.J. Czernik ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Marrow Fat ◽  
Bone Marrow Fat ◽  
Brown Adipose ◽  
Tissue Characteristics

scholarly journals Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

2021 ◽  
Vol 22 (12) ◽  
pp. 6429
Author(s):  
Xia Xu ◽  
Shuyu Liu ◽  
Hua Liu ◽  
Kang Ru ◽  
Yunxian Jia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Cells ◽  
Current Knowledge ◽  
Bone Diseases ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Cellular Mechanotransduction ◽  
Piezo Channels ◽  
And Function

Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. Emerged as key molecular detectors of mechanical forces, Piezo channels’ functions in bone have attracted more and more attention. Here, we summarize the current knowledge of Piezo channels and review the research advances of Piezo channels’ function in bone by highlighting Piezo1′s role in bone cells, including osteocyte, bone marrow mesenchymal stem cell (BM-MSC), osteoblast, osteoclast, and chondrocyte. Moreover, the role of Piezo channels in bone diseases is summarized.

Obesity and SARS-CoV-2 Infection a Multifaceted Interplay - Adipose Tissue Inflammation, Adipokine Disbalance and Immunity

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Cherneva RV ◽  
◽  
Valev D ◽  
Cherneva ZV ◽  
◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Viral Infections ◽  
Cell Number ◽  
Overweight And Obesity ◽  
Inflammasome Activation ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Insulin Resistant ◽  
And Function

Overweight and obesity are the most common comorbidities in SARSCoV- 2 patients, requiring hospitalization in intensive care units. The multifaceted nature of obesity including its effects on respiratory mechanics and immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Most coronaviruses overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. Hyperleptinemia, insulin resistance and adipose tissue inflammation are hallmarks of obesity, which is associated with a leptin and insulin resistant state. Leptin regulates appetite and metabolism and through the Jak/STAT and Akt pathways modulates T cell number and function; insulin receptor signaling is closely engaged in T cell proliferation, whereas low garde adipose tissue inflammation provokes aberrant inflammasome activation. The review discusses these phenomena. It presents the reasons for susceptibility to respiratory viral infections in obese patients, as well as, the immunomodulatory effects of obesity to the outcome.

I Can Get Fat Where? The Other Types of Fat

2021 ◽  
pp. 91-120
Author(s):  
Nathan Denton
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
The Other ◽  
Human Biology ◽  
Potential Contribution ◽  
Marrow Fat ◽  
Bone Marrow Fat ◽  
Bone Marrow Adipose Tissue ◽  
White Fat ◽  
The Relationship

This chapter considers the more obscure non-white types of adipose tissue present in the human body. The first and better-known type discussed is brown fat, which contributes to the regulation of body temperature as it burns (excess) calories to generate heat. The second section explores the biology of bone marrow fat, whose enigmatic behaviour in the context of starvation and obesity does little to help define its role. After considering the relationship between bone marrow adipose tissue, bone strength, and overall metabolic health, this chapter concludes by briefly reviewing other, lesser-known types of (white) fat (e.g., epicardial fat) and their potential contribution to human biology.

scholarly journals Active Cushing syndrome patients have increased ectopic fat deposition and bone marrow fat content compared to cured patients and healthy subjects: a pilot 1H-MRS study

2018 ◽  
Vol 179 (5) ◽  
pp. 307-317 ◽  
Author(s):  
F Maurice ◽  
A Dutour ◽  
C Vincentelli ◽  
I Abdesselam ◽  
M Bernard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cushing Syndrome ◽  
Cross Sectional Study ◽  
Mineral Density ◽  
Marrow Fat ◽  
1H Mrs ◽  
Cross Sectional ◽  
Bone Marrow Fat ◽  
Main Regulator

Objective Glucocorticoid excess is one of the most important causes of bone disorders. Bone marrow fat (BMF) has been identified as a new mediator of bone metabolism. Cushing syndrome (CS) is a main regulator of adipose tissue distribution but its impact on BMF is unknown. The objective of the study was to evaluate the effect of chronic hypercortisolism on BMF. Design This was a cross-sectional study. Seventeen active and 17 cured ACTH-dependent CS patients along with 17 controls (matched with the active group for age and sex) were included. Methods The BMF content of the femoral neck and L3 vertebrae were measured by 1H-MRS on a 3-Tesla wide-bore magnet. Bone mineral density (BMD) was evaluated in patients using dual-energy X-ray absorptiometry. Results Active CS patients had higher BMF content both in the femur (82.5 ± 2.6%) and vertebrae (70.1 ± 5.1%) compared to the controls (70.8 ± 3.6%, P = 0.013 and 49.0 ± 3.7% P = 0.005, respectively). In cured CS patients (average remission time of 43 months), BMF content was not different from controls at both sites (72.3 ± 2.9% (femur) and 46.7% ± 5.3% (L3)). BMF content was positively correlated with age, fasting plasma glucose, HbA1c, triglycerides and visceral adipose tissue in the whole cohort and negatively correlated with BMD values in the CS patients. Conclusions Accumulation of BMF is induced by hypercortisolism. In remission patients, BMF reached values of controls. Further studies are needed to determine whether this increase in marrow adiposity in CS is associated with bone loss.

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