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Article ; Online: Nutrient regulation of bone marrow adipose tissue: skeletal implications of weight loss.

Rosen, Clifford J / Horowitz, Mark C

2023 Volume 19, Issue 11, Page(s) 626–638

Abstract: Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone ... ...

Abstract	Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered.
MeSH term(s)	Humans ; Adipocytes/physiology ; Adipose Tissue ; Bone Marrow/pathology ; Bone Marrow/physiology ; Bone Marrow Cells/physiology ; Obesity/pathology ; Weight Loss
Language	English
Publishing date	2023-08-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/s41574-023-00879-4
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Article: Intermittent Methionine Restriction Reduces Marrow Fat Accumulation and Preserves More Bone Mass than Continuous Methionine Restriction.

Plummer, Jason D / Horowitz, Mark C / Johnson, Jay E

Aging Biology

2024 Volume 2

Abstract: ... health benefits to the continuous intervention but does so without markedly deleterious effects ...

Abstract	Continuous methionine restriction (MR) is one of only a few dietary interventions known to dramatically extend mammalian healthspan. For example, continuously methionine-restricted rodents show less age-related pathology and are up to 45% longer-lived than controls. Intriguingly, MR is feasible for humans, andanumberofstudieshavesuggestedthatmethionine-restrictedindividualsmayreceivesimilarhealthspan benefits as rodents. However, long-term adherence to a continuously methionine-restricted diet is likely to be challenging (or even undesirable) for many individuals. To address this, we previously developed an intermittent version of MR (IMR) and demonstrated that it confers nearly identical metabolic health benefits to mice as the continuous intervention, despite having a relatively short interventional period (i.e., only three days per week). We also observed that female mice undergoing IMR show a more pronounced amelioration of diet-induced dysglycemia than continuously methionine-restricted counterparts, while male mice undergoing IMR retain more lean body mass as compared with continuously methionine-restricted controls. Prompted by such findings, we sought to determine other ways in which IMR might compare favorably with continuous MR. While it is known that continuous MR has deleterious effects on bone in mice, including loss of both trabecular and cortical bone, we considered that mice undergoing IMR might retain more bone mass. Here, we report that, as compared with continuous MR, IMR results in a preservation of both trabecular and cortical bone, as well as a dramatic reduction in the accumulation of marrow fat. Consistent with such findings, mechanical testing revealed that the bones of intermittently methionine-restricted mice are significantly stronger than those of mice subjected to the continuous intervention. Finally, static histomorphometric analyses suggest that IMR likely results in more bone mass than that produced by continuous MR, primarily by increasing the number of osteoblasts. Together, our results demonstrate that the more practicable intermittent form of MR not only confers similar metabolic health benefits to the continuous intervention but does so without markedly deleterious effects on either the amount or strength of bone. These data provide further support for the use of IMR in humans.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
DOI	10.59368/agingbio.20230019
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Article ; Online: Corrigendum: Brief research report: impact of vaccination on antibody responses and mortality from severe COVID-19.

Adhikari, Bindu / Bednash, Joseph S / Horowitz, Jeffrey C / Rubinstein, Mark P / Vlasova, Anastasia N

Frontiers in immunology

2024 Volume 15, Page(s) 1384209

Abstract: This corrects the article DOI: 10.3389/fimmu.2024.1325243.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2024.1325243.].
Language	English
Publishing date	2024-02-28
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1384209
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Article ; Online: Brief research report: impact of vaccination on antibody responses and mortality from severe COVID-19.

Adhikari, Bindu / Bednash, Joseph S / Horowitz, Jeffrey C / Rubinstein, Mark P / Vlasova, Anastasia N

Frontiers in immunology

2024 Volume 15, Page(s) 1325243

Abstract: Introduction: While it is established that vaccination reduces risk of hospitalization, there is conflicting data on whether it improves outcome among hospitalized COVID-19 patients. This study evaluated clinical outcomes and antibody (Ab) responses to ... ...

Abstract	Introduction: While it is established that vaccination reduces risk of hospitalization, there is conflicting data on whether it improves outcome among hospitalized COVID-19 patients. This study evaluated clinical outcomes and antibody (Ab) responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection/vaccines in patients with acute respiratory failure (ARF) and various comorbidities. Methods: In this single-center study, 152 adult patients were admitted to Ohio State University hospital with ARF (05/2020 - 11/2022) including 112 COVID-19-positive and 40 COVID-19-negative patients. Of the COVID-19 positive patients, 23 were vaccinated for SARS-CoV-2 (Vax), and 89 were not (NVax). Of the NVax COVID-19 patients, 46 were admitted before and 43 after SARS-CoV-2 vaccines were approved. SARS-CoV-2 Ab levels were measured/analyzed based on various demographic and clinical parameters of COVID-19 patients. Additionally, total IgG4 Ab concentrations were compared between the Vax and NVax patients. Results: While mortality rates were 36% (n=25) and 27% (n=15) for non-COVID-19 NVax and Vax patients, respectively, in COVID-19 patients mortality rates were 37% (NVax, n=89) and 70% (Vax, n=23). Among COVID-19 patients, mortality rate was significantly higher among Vax vs. NVax patients (p=0.002). The Charlson's Comorbidity Index score (CCI) was also significantly higher among Vax vs. NVax COVID-19 patients. However, the mortality risk remained significantly higher (p=0.02) when we compared COVID-19 Vax vs. NVax patients with similar CCI score, suggesting that additional factors may increase risk of mortality. Higher levels of SARS-CoV-2 Abs were noted among survivors, suggestive of their protective role. We observed a trend for increased total IgG4 Ab, which promotes immune tolerance, in the Vax vs. NVax patients in week 3. Conclusion: Although our cohort size is small, our results suggest that vaccination status of hospital-admitted COVID-19 patients may not be instructive in determining mortality risk. This may reflect that within the general population, those individuals at highest risk for COVID-19 mortality/immune failure are likely to be vaccinated. Importantly, the value of vaccination may be in preventing hospitalization as opposed to stratifying outcome among hospitalized patients, although our data do not address this possibility. Additional research to identify factors predictive of aberrant immunogenic responses to vaccination is warranted.
MeSH term(s)	Adult ; Humans ; COVID-19 ; SARS-CoV-2 ; Antibody Formation ; COVID-19 Vaccines ; Research Report ; Vaccination ; Immunoglobulin G
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin G
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1325243
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Article ; Online: Antipsychotic maintenance treatment versus dose reduction: how the story continues.

Sommer, Iris E C / Horowitz, Mark / Allott, Kelly / Speyer, Helene / Begemann, Marieke J H

The lancet. Psychiatry

2022 Volume 9, Issue 8, Page(s) 602–603

MeSH term(s)	Antipsychotic Agents/therapeutic use ; Drug Administration Schedule ; Drug Tapering ; Humans ; Schizophrenia/drug therapy
Chemical Substances	Antipsychotic Agents
Language	English
Publishing date	2022-06-23
Publishing country	England
Document type	Journal Article ; Comment
ISSN	2215-0374
ISSN (online)	2215-0374
DOI	10.1016/S2215-0366(22)00230-9
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Article ; Online: Fat and Bone: PGC-1α Regulates Mesenchymal Cell Fate during Aging and Osteoporosis.

Horowitz, Mark C / Tommasini, Steven M

Cell stem cell

2018 Volume 23, Issue 2, Page(s) 151–153

Abstract: PGC-1α is a transcriptional co-activator associated with PPARγ that regulates thermogenic gene expression in brown fat. In this issue, Yu et al. (2018) show that PGC-1α regulates marrow mesenchymal stromal cell lineage allocation in vivo, inhibiting ... ...

Abstract	PGC-1α is a transcriptional co-activator associated with PPARγ that regulates thermogenic gene expression in brown fat. In this issue, Yu et al. (2018) show that PGC-1α regulates marrow mesenchymal stromal cell lineage allocation in vivo, inhibiting marrow adipogenesis and associated bone loss in the aging skeleton and following ovariectomy-induced osteoporosis.
MeSH term(s)	Adipogenesis ; Adipose Tissue, Brown ; Cell Differentiation ; Female ; Humans ; Mesenchymal Stem Cells ; Osteoporosis ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Chemical Substances	Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Language	English
Publishing date	2018-08-03
Publishing country	United States
Document type	Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2018.07.010
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Article ; Online: Cystine rather than cysteine is the preferred substrate for β-elimination by cystathionine γ-lyase: implications for dietary methionine restriction.

Jeitner, Thomas M / Azcona, Juan A / Ables, Gene P / Cooke, Diana / Horowitz, Mark C / Singh, Pradeep / Kelly, James M / Cooper, Arthur J L

GeroScience

2023

Abstract: Dietary methionine restriction (MR) increases longevity by improving health. In experimental models, MR is accompanied by decreased cystathionine β-synthase activity and increased cystathionine γ-lyase activity. These enzymes are parts of the ... ...

Abstract	Dietary methionine restriction (MR) increases longevity by improving health. In experimental models, MR is accompanied by decreased cystathionine β-synthase activity and increased cystathionine γ-lyase activity. These enzymes are parts of the transsulfuration pathway which produces cysteine and 2-oxobutanoate. Thus, the decrease in cystathionine β-synthase activity is likely to account for the loss of tissue cysteine observed in MR animals. Despite this decrease in cysteine levels, these tissues exhibit increased H
Language	English
Publishing date	2023-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-00788-4
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Article ; Online: Fat Decisions: Leptin Regulates Bone versus Fat in the Marrow.

Rodeheffer, Matthew S / Horowitz, Mark C

Cell stem cell

2016 Volume 18, Issue 6, Page(s) 684–686

Abstract: Leptin is an adipocyte-derived hormone involved in energy sensing. In this issue of Cell Stem Cell, Yue et al. (2016) show that leptin is a physiologic signal that acts directly on Leptin-Receptor-expressing mesenchymal stromal cells in adult bone marrow ...

Abstract	Leptin is an adipocyte-derived hormone involved in energy sensing. In this issue of Cell Stem Cell, Yue et al. (2016) show that leptin is a physiologic signal that acts directly on Leptin-Receptor-expressing mesenchymal stromal cells in adult bone marrow to influence their lineage allocation in vivo, inhibiting bone formation and inducing marrow adipogenesis.
MeSH term(s)	Adipocytes/drug effects ; Adipogenesis/drug effects ; Bone Marrow/drug effects ; Bone Marrow Cells/drug effects ; Bone and Bones/drug effects ; Leptin ; Mesenchymal Stem Cells/drug effects
Chemical Substances	Leptin
Language	English
Publishing date	2016-05-26
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2016.05.006
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Article ; Online: Long-term outcomes after unrelated donor transplantation for severe sickle cell disease on the BMT CTN 0601 trial.

American journal of hematology

2024 Volume 99, Issue 4, Page(s) 785–788

MeSH term(s)	Humans ; Unrelated Donors ; Bone Marrow Transplantation ; Hematopoietic Stem Cell Transplantation ; Anemia, Sickle Cell/therapy ; Graft vs Host Disease
Language	English
Publishing date	2024-02-11
Publishing country	United States
Document type	Letter
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27251
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Article ; Online: Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

Lee, David J / El-Khoury, Habib / Tramontano, Angela C / Alberge, Jean-Baptiste / Perry, Jacqueline / Davis, Maya I / Horowitz, Erica / Redd, Robert / Sakrikar, Dhananjay / Barnidge, David / Perkins, Mark C / Harding, Stephen / Mucci, Lorelei / Rebbeck, Timothy R / Ghobrial, Irene M / Marinac, Catherine R

Blood advances

2024 Volume 8, Issue 7, Page(s) 1737–1746

Abstract: Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate ...

Abstract	Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.
MeSH term(s)	Humans ; Monoclonal Gammopathy of Undetermined Significance/diagnosis ; Monoclonal Gammopathy of Undetermined Significance/epidemiology ; Monoclonal Gammopathy of Undetermined Significance/complications ; Multiple Myeloma/diagnosis ; Multiple Myeloma/epidemiology ; Multiple Myeloma/etiology ; Obesity/complications ; Obesity/diagnosis ; Obesity/epidemiology ; Risk Factors
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010843
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