Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids

Wu, Chia‐Lung; Diekman, Brian O.; Jain, Deeptee; Guilak, Farshid

doi:10.1038/ijo.2012.171

Cited by 93 publications

(101 citation statements)

References 59 publications

(66 reference statements)

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“…Furthermore, response of BMSCs to nutrient stress might be different compared to stem cells from other sites. For example, adult stem cells respond to increased levels of free fatty acids in a site-specific manner 37 .…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

et al. 2016

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OBJECTIVEAlthough intrauterine nutritional stress is known to result in offspring obesity and metabolic phenotype, the underlying cellular/molecular mechanisms remain incompletely understood.We tested the hypothesis that compared to the controls, the bone marrow-derived mesenchymal stem cells (BMSCs) of the intrauterine growth restricted (IUGR) offspring exhibit to a more adipogenic phenotype.METHODSA well-established rat model of maternal food restriction (MFR), i.e., 50% global caloric restriction during the later-half of pregnancy and ad libitum diet following birth that is known to result in an obese offspring with a metabolic phenotype was used. BMSCs at 3 weeks of age were isolated, and then molecularly and functionally profiled.RESULTSBMSCs of the intrauterine nutritionally-restricted offspring demonstrated an increased proliferation and an enhanced adipogenic molecular profile at miRNA, mRNA and protein levels, with an overall up-regulated PPARγ (miR-30d, miR-103, PPARγ, C/EPBα, ADRP, LPL, SREBP1), but down-regulated Wnt (LRP5, LEF-1, β-catenin, ZNF521 and RUNX2) signaling profile. Following adipogenic induction, compared to the control BMSCs, the already up-regulated adipogenic profile of the MFR BMSCs, showed a further increased adipogenic response.CONCLUSIONSMarkedly enhanced adipogenic molecular profile and increased cell proliferation of MFR BMSCs suggest a possible novel cellular/mechanistic link between the intrauterine nutritional stress and offspring metabolic phenotype including obesity, providing new potential predictive and therapeutic targets against these conditions in the IUGR offspring.

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Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

et al. 2016

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“…On the other hand, HFD alters the differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs), and infrapatellar fat pad-derived stem cells (IFP). Notably, the fatty acid constituents of the diet in part mediated this effect, implicating a possible role for PPAR-δ signaling (48). Also, the impact of a HFD in hematopoiesis is context dependent.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-δ Pathway

Beyaz

Yılmaz

2016

Clinical Cancer Research

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Peroxisome Proliferator-Activated Receptor delta (PPAR-δ) is a nuclear receptor transcription factor that regulates gene expression during development and disease states such as cancer. However, the precise role of PPAR-δ during tumorigenesis is not well understood. Recent data suggest that PPAR-δ may have context specific oncogenic and tumor suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example in the intestine, pro-obesity diets, like a high fat diet (HFD), are associated with increased colorectal cancer incidence. Interestingly, many of the effects of a HFD in the stem and progenitor cell compartment are driven by a robust PPAR-δ program and contribute to the early steps of intestinal tumorigenesis. Importantly, the PPAR-δ pathway or its downstream mediators may serve as therapeutic intervention points or biomarkers in colon cancer that particularly arise in obese patients. Although potent PPAR-δ agonists and antagonists exist, their clinical utility may be enhanced by uncovering how PPAR-δ mediates tumorigenesis in diverse tissues and cell-types as well as in response to diet.

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“…61 Concurrent with increases in total body and visceral adiposity, high-fat diet models of obesity in rodents show increased marrow fat, 47,62 increased commitment to adipogenesis, and alterations in MSC differentiation potential. 63 MSC differentiation is also regulated by the Wnt signaling pathway, 64–66 and it is understood that osteoblastogenesis and adipogenesis in the marrow generally maintain an inverse relationship. Adipocyte commitment is often associated with reduced bone formation, as seen in models of microgravity, 67,68 ovarian hormone depletion, 69,70 and aging.…”

Section: Impact Of Obesity On Musculoskeletal Tissue Systemsmentioning

confidence: 99%

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

Frechette

Krishnamoorthy

Pamon

et al. 2017

Annals of the New York Academy of Sciences

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The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type 2 diabetes, heart disease, fatty liver disease, and cancer. The impact of excess fat on musculoskeletal health is still unclear, although it is associated with increased fracture risk and a decline in muscular function. The complexity of obesity makes understanding the etiology of bone and muscle abnormalities difficult. Exercise is an effective and commonly prescribed non-pharmacological treatment option, but it can be difficult or unsafe for the frail, elderly, and morbidly obese. Exercise alternatives, such as low-intensity vibration (LIV), have potential for improving musculoskeletal health, particularly in conditions with excess fat. LIV has been shown to influence bone marrow mesenchymal stem cell differentiation toward higher-order tissues (i.e., bone) and away from fat. While the exact mechanisms are not fully understood, recent studies utilizing LIV both at the bench and in the clinic have demonstrated its efficacy. Here, we discuss the current literature investigating the effects of obesity on bone, muscle, and bone marrow and how exercise and LIV can be used as effective treatments for combating the negative effects in the presence of excess fat.

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Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids

Cited by 93 publications

References 59 publications

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-δ Pathway

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

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