Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice

Park, Byong‐Gon; Park, Yoon‐Sun; Park, Joo Woong; Shin, Eunji; Shin, Woon‐Seob

doi:10.1016/j.bbrc.2016.03.098

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…However, clues are provided by previous reports. For example, extracellular RHAMM binds to HA fragments in the size range that has recently been reported to suppress adipogenesis[74, 75] and associates with transmembrane receptors such as CD44 and PDGFR[73, 76, 77] to regulate activation of ERK1,2 signaling pathways controlling mesenchymal differentiation [73, 77]. Furthermore, intracellular RHAMM protein isoforms complex with, sustain activity and regulate subcellular targeting of the MEK1/ERK1,2 complexes that affect adipogenesis [38].…”

Section: Discussionmentioning

confidence: 99%

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

et al. 2017

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Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes. Oil red O uptake into fat droplets and adiponectin production were used as biomarkers of adipogenesis. Positive peptides were formulated in either collagen I or hyaluronan (Orthovisc) gels then assessed for their adipogenic potential in vivo following injection into dorsal rat skin and mammary fat pads. Fat content was quantified and characterized using micro CT imaging, morphometry, histology, RT-PCR and ELISA analyses of adipogenic gene expression. Injection of screened peptides increased dorsal back subcutaneous fat pad area (208.3 ± 10.4 mm2 versus control 84.11 ± 4.2 mm2; p < 0.05) and mammary fat pad size (45 ± 11 mg above control background, p=0.002) in female rats. This effect lasted >5 weeks as detected by micro CT imaging and perilipin 1 mRNA expression. RHAMM expression suppresses while blocking peptides promote expression of PPARγ, C/EBP and their target genes. Blocking RHAMM function by peptide injection or topical application is a novel and minimally invasive method for potentially promoting subcutaneous adipogenesis in lipodystrophic diseases and a complementary tool to subcutaneous fat augmentation techniques.

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Section: Discussionmentioning

confidence: 99%

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

et al. 2017

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“…Oral administration of these HA fragments decreased body weight, adipose tissues, serum lipid (low-density lipoprotein cholesterol, triglyceride), and leptin levels in mice fed on a high-fat diet. HA fragments also decreased the hypertrophy of adipose tissue and ameliorated liver steatosis, showing a strong anti-obesity and anti-diabetic effect, possibly through enhancing PPARα and suppressing PPARγ expression [77]. It is important to note that the orally administrated HA may not enter circulation, so the site of action for the HA used in this study may be the intestinal digestive track.…”

Section: Hyaluronan In Adipose Tissue and Systemic Metabolismmentioning

confidence: 99%

Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism

Zhu

Kruglikov²,

Akgul

et al. 2019

Matrix Biology

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Hyaluronic acid (HA, also known as hyaluronan), is a non-sulfated linear glycosaminoglycan polymer consisting of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine abundantly present in the extracellular matrix. The sizes of hyaluronic acid polymers range from 5000 to 20,000,000 Da in vivo, and the functions of HA are largely dictated by its size. Due to its high biocompatibility, HA has been commonly used as soft tissue filler as well as a major component of biomaterial scaffolds in tissue engineering. Several studies have implicated that HA may promote differentiation of adipose tissue derived stem cells in vitro or in vivo when used as a supporting scaffold. However, whether HA actually promotes adipogenesis in vivo and the subsequent metabolic effects of this process are unclear. This review summarizes some recent publications in the field and discusses the possible directions and approaches for future studies, focusing on the role of HA in the adipose tissue.

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“…WAT stores excessive energy as triglycerides, while BAT decreases energy storage by generating heat 22 . UCP-1 and UCP-2 induce the oxidation and ADP phosphorylation, decrease ATP production, and increase energy consumption and heat yield, eventually leading to weight loss 9,26,27 .…”

Section: Discussionmentioning

confidence: 99%

Transgenic n-3 PUFAs Enrichment Regulates Related Physiological Activities by Affecting Nerves

Song¹,

Zhang²

2019

ijSciences

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Obesity is generally defined as an excess of body fats and related to weight gain. The hypothalamic arcuate nucleus (ARC) is responsible for regulating peripheral signals that control food intake and energy balance. Uncoupling protein-1 (UCP-1) and UCP-2 are related-genes that adjust body weight. The aim of this study is to explore the effect of fat-1 gene on body weight. We found that the weight/length ratios of fat-1 transgenic mice were smaller than wild-type (WT) mice. We hypothesized that an increase in the levels of n-3 PUFAs might alter the expression of hypothalamic neuropeptide and lead to weight loss in fat-1 mice because fat-1 gene transforms n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. Therefore, the appetite-regulating neuropeptides in the hypothalamic ARC, including neuropeptide Y (NPY), agouti-related peptides (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), and ghrelin, were measured by Immunofluorescence. The mRNA levels of UCP-1 in brown adipose tissues and UCP-2 in white adipose tissues were measured by RT-PCR. The protein levels of UCP-2 in white adipose tissues also were measured by Western Blot. Compared with WT mice, the levels of CART, POMC and ghrelin increased, the levels of NPY and AgRP decreased, whereas the mRNA levels of UCP-1, UCP-2 increased, the protein levels of UCP-2 increased in fat-1 mice. The results indicated that the fat-1 gene or n-3 PUFAs participate in inhibition of body weight by regulating the expressions of appetite neuropeptide and uncoupling protein.

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Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice

Cited by 15 publications

References 29 publications

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism

Transgenic n-3 PUFAs Enrichment Regulates Related Physiological Activities by Affecting Nerves

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