Immortal Brown Adipocytes fromp53-Knockout Mice: Differentiation and Expression of Uncoupling Proteins

Irie, Yukiko; Asano, Atsushi; Cañas, Xavier; Nikami, Hideki; Aizawa, Shinichi; Saito, Masayuki

doi:10.1006/bbrc.1998.9999

Cited by 63 publications

(62 citation statements)

References 19 publications

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“…The potential of the CD34ϩ cells to differentiate into brown adipocytes was preserved throughout development and aging, although the UCP1/leptin ratio became smaller after expansion of the cells, suggesting a shift toward a white adipocyte phenotype. In immortalized HB2 brown adipocytes, UCP1 mRNA expression was found to diminish gradually upon repeated passages [37]. This loss and that observed in this study could be due to a negative growth advantage of cells with uncoupled respiration.…”

Section: Discussionsupporting

confidence: 61%

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

et al. 2008

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Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-␥ (PPAR␥) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR␥ agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.

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Section: Discussionsupporting

confidence: 61%

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

et al. 2008

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“…HB2 cells (kindly provided by Prof. Masayuki Saito) were isolated from BAT of p53 knockout mice and were differentiated into mature brown adipocytes, as described previously (24). In short, HB2 cells were seeded on collagen-coated dish and cultured in high-glucose medium (Sigma-Aldrich, Tokyo, Japan) supplemented with 10% fetal bovine serum (Invitrogen) and 1% penicillin-streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Effects of dietary phosphate on glucose and lipid metabolism

Abuduli

Ohminami

Otani

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Recent epidemiological and animal studies have suggested that excess intake of phosphate (Pi) is a risk factor for the progression of chronic kidney disease and its cardiovascular complications. However, little is known about the impact of dietary high Pi intake on the development of metabolic disorders such as obesity and type 2 diabetes. In this study, we investigated the effects of dietary Pi on glucose and lipid metabolism in healthy rats. Male 8-wk-old Sprague-Dawley rats were divided into three groups and given experimental diets containing varying amounts of Pi, i.e., 0.2 [low Pi (LP)], 0.6 [control Pi (CP)], and 1.2% [high Pi (HP)]. After 4 wk, the HP group showed lower visceral fat accumulation compared with other groups, accompanied by a low respiratory exchange ratio (V CO2/V O2) without alteration of locomotive activity. The HP group had lower levels of plasma insulin and nonesterified fatty acids. In addition, the HP group also showed suppressed expression of hepatic lipogenic genes, including sterol regulatory element-binding protein-1c, fatty acid synthase, and acetyl-CoA carboxylase, whereas there was no difference in hepatic fat oxidation among the groups. On the other hand, uncoupling protein (UCP) 1 and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) expression were significantly increased in the brown adipose tissue (BAT) of the HP group. Our data demonstrated that a high-Pi diet can negatively regulate lipid synthesis in the liver and increase mRNA expression related to lipid oxidation and UCP1 in BAT, thereby preventing visceral fat accumulation. Thus, dietary P i is a novel metabolic regulator. dietary phosphate; energy metabolism; brown adipose tissue; visceral fat OBESITY CONTINUES TO BE A MAJOR PUBLIC HEALTH PROBLEM worldwide. Overnutrition and an increased consumption of fast foods are primary factors contributing to this problem. Fast foods or processed foods have high energy density and also frequently contain a large amount of P i as a food additive. Recent epidemiological studies have suggested that a high dietary P i intake can be associated with increased cardiovascular risk and other metabolic disorders.P i is an essential nutrient that significantly affects skeletal formation, energy metabolism, and intracellular signaling (43,45). P i homeostasis is regulated by the absorption of P i in the intestine, bone formation/resorption, and reabsorption of P i in the kidney. The kidney is particularly important in the regulation of P i homeostasis (36, 45). Most P i -regulating factors, such as high/low P i intake, 1,25-dihydroxyvitamin D [1,25(OH) 2 D], parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), can regulate P i reabsorption in the kidney to maintain the P i homeostasis (6, 36, 43).Recent epidemiological and animal studies have suggested that an excessive intake of P i is a risk factor for the progression of chronic kidney disease and the occurrence of cardiovascular complications (8, 45). Excess P i has been independently associated with ...

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“…HB2 and HW cells were prepared from interscapular BAT and epididymal WAT, respectively, of p53 homozygous knockout mice as described previously (16). The cells were maintained in DMEM (Sigma-Aldrich) supplemented with 10% FBS (JRH Biosciences), streptomycin (50 μg/ml), and penicillin (50 U/ml).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we further examined the expression of FSP27 in brown adipocyte (HB2) and white adipocyte (HW) cell lines that were established from preadipocytes of BAT and WAT, from mice deficient in the tumor suppressor p53 (16). After induction of adipogenesis, HB2 and HW cells show morphological characteristics of brown and white adipocytes, including the formation of small and large lipid droplets in the cytoplasm, respectively (Supplemental Figure 3).…”

Section: Figurementioning

confidence: 99%

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

Nishino¹,

Tamori²,

Tateya³

et al. 2008

J. Clin. Invest.

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245

375

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White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

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Immortal Brown Adipocytes fromp53-Knockout Mice: Differentiation and Expression of Uncoupling Proteins

Cited by 63 publications

References 19 publications

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

Effects of dietary phosphate on glucose and lipid metabolism

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

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