Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation

Kubo, Nobuhiko; Kawahara, Mio; Okamatsu‐Ogura, Yuko; Miyazaki, Yosuke; Otsuka, Ryuto; Fukuchi, Kazuki

doi:10.1007/s11307-018-1251-6

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…The arcuate nucleus NPY regulates various physiological functions, including BAT thermogenesis (35). BAT contains abundant mitochondria and shows high expression of UCP1, which increase heat energy dissipation (36). Previous studies found that the Arc-specific NPY signaling pathway decreased sympathetically innervated BAT thermogenesis by down-regulating of UCP1 expression and BAT temperature (37).…”

Section: Discussionmentioning

confidence: 99%

Hyperbaric Oxygen Ameliorates Insulin Sensitivity by Increasing GLUT4 Expression in Skeletal Muscle and Stimulating UCP1 in Brown Adipose Tissue in T2DM Mice

et al. 2020

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Hyperbaric oxygen (HBO) therapy is a treatment modality useful for diseases. Hypoxia could stimulate the induction of insulin resistance. Therefore, we sought to determine whether hyperbaric oxygen would ameliorate insulin sensitivity by promoting glucose transporter type 4 (GLUT4) expression in muscle and by stimulating UCP1 in brown adipose tissue (BAT) in a streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) mouse model. Male C57BL/6J mice were treated three times with low-dose of streptozocin (60 mg/kg, i.p.) and were fed with high-fat diets (HFD) to establish the T2DM model. HBO was administered daily as 100% oxygen at 2.0 atmosphere absolute (ATA) for 1 h for a week. We found that HBO significantly reduced blood glucose levels and attenuated insulin resistance in T2DM mice. HBO modulated food intake by influencing the activity of neuropeptide Y (NPY)-positive neurons in the arcuate nucleus (Arc). HBO treatment increased GLUT4 amount and level of phosphorylated Akt (p-Akt) in muscles of T2DM mice whereas this treatment stimulated the phosphorylation of AMPK in muscles of both T2DM and HFD mice. The morphological staining of BAT and the increased expression of uncoupling of protein 1 (UCP1) demonstrated the promotion of metabolism after HBO treatment. These findings suggest that HBO ameliorates insulin sensitivity of T2DM mice by stimulating the Akt signaling pathway and by promoting GLUT4 expression in muscle, and by increasing UCP1 expression in BAT.

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Section: Discussionmentioning

confidence: 99%

Hyperbaric Oxygen Ameliorates Insulin Sensitivity by Increasing GLUT4 Expression in Skeletal Muscle and Stimulating UCP1 in Brown Adipose Tissue in T2DM Mice

et al. 2020

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“…Obesity impairs b3-adrenergic agonist-dependent brown and beige adipocyte activation (Kubo et al, 2019;Shin et al, 2019). Next, we asked whether asparagine supplementation enhanced adipose tissue response to b3-adrenergic agonist in diet-induced obese mice.…”

Section: Asparagine Feeding Nourishes Thermogenesis In Adipose Tissuesmentioning

confidence: 99%

Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues

Shi

Cui

et al. 2021

The EMBO Journal

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Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine-fed mice showed better cold tolerance. In mice with diet-induced obesity, the asparagine-fed group was more responsive to b3-adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and 13 C-glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.

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“…Additionally, Cypess et al con rmed the presence of adipose tissue such as brown fat in adult humans when exposed to cold [10]. BAT activation and WAT browning accelerates glycolipid intake, reduces the requirement for insulin secretion, and improves glycolipid metabolism and insulin resistance in patients with obesity and type 2 diabetes [11][12][13]. The thermogenic activity of BAT is largely dependent on uncoupling protein 1 (UCP1), which is present in the inner mitochondrial membrane.…”

Section: Introductionmentioning

confidence: 99%

Hederagenin from Hedera helix promotes fat browning in 3T3-L1 adipocytes

Choi,

Lee,

Lim

et al. 2024

Preprint

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Background Currently, the regulation of energy homeostasis through increased energy consumption is attracting attention to treat obesity. White adipose tissue is known to play a role in accumulating energy by storing excess energy, while brown adipose tissue consumes energy and maintains body temperature. Thus, the browning of white adipose tissue has been confirmed to be effective in controlling obesity. Hedera helix (H. helix) has been widely used as a traditional medicine for various diseases. In several previous studies, hederagenin (HDG) from H. helix has demonstrated many biological activities. In this study, we investigated the anti-obesity effect of HDG on fat browning in 3T3-L1 adipocytes. Methods Cytotoxicity was assessed in 3T3-L1 cells through the Dimethyl sulfoxide and thiazolyl blue tetrazolium bromide (MTT) assay, while the extent of lipid accumulation was compared using the Oil red O (ORO) assay. Protein expression and mRNA expression were compared using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results Consequent to HDG treatment, a reduction in lipid accumulation was confirmed through oil red O staining. In addition, this study confirmed that HDG increases heat production by upregulating the expression of several targets related to thermogenesis, including uncoupling protein 1 (UCP1). This process is closely related to the inhibition of lipogenesis through the adenosine monophosphate-activated protein kinase (AMPK) phosphorylation signaling pathway and lipolysis through the protein kinase A (PKA) signaling pathway. Conclusions HDG is expected to be effective in promoting fat browning, indicating its potential as a natural anti-obesity candidate.

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Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation

Abstract: The metabolic response against adrenergic stimulation varied depending on the type of adipose tissue and DM. This could be important for the therapeutic activation of adipose tissue metabolism in obese diabetic patients.

Cited by 12 publications

References 35 publications

Hyperbaric Oxygen Ameliorates Insulin Sensitivity by Increasing GLUT4 Expression in Skeletal Muscle and Stimulating UCP1 in Brown Adipose Tissue in T2DM Mice

Hyperbaric Oxygen Ameliorates Insulin Sensitivity by Increasing GLUT4 Expression in Skeletal Muscle and Stimulating UCP1 in Brown Adipose Tissue in T2DM Mice

Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues

Hederagenin from Hedera helix promotes fat browning in 3T3-L1 adipocytes

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