A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

Shu, Lingling; Hoo, Ruby L.C.; Wu, Xiaoping; Pan, Yong; Lee, Ida P. C.; Cheong, Lai Yee; Bornstein, Stefan R.; Rong, Xianglu; Guo, Jiao; Xu, Aimin

doi:10.1038/ncomms14147

Cited by 81 publications

(66 citation statements)

References 72 publications

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“…Mechanistically, the potential mechanism underlying the different effect of UA on mice body weight under an HFD and a chow diet might be due to tissue levels of T3, which is relatively low and may not reach concentrations at which it could significantly activate the thermogenic program in BAT and iWAT under normal diet feeding. Instead, higher levels of T3 were shown in UA-treated HFD mice than in normal-diet-feeding mice (Fig 5D and 5E (S12D-S12F Fig) [62], results derived from prelimin HFD increases tissue levels of T3 [66]. In fact, several similar lines of…”

Section: Plos Biologymentioning

confidence: 85%

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

et al. 2020

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Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

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Section: Plos Biologymentioning

confidence: 85%

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

et al. 2020

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“…Primary stromal vascular fraction (SVF) was isolated as described previously 30 with some modifications. Briefly, wild-type C57BL/6 mice were sacrificed and the adipose tissues were processed to obtain stromal vascular fractions (SVFs).…”

Section: Stromal Vascular Fraction Isolationmentioning

confidence: 99%

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

Peng

Zeng

et al. 2020

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Purpose: Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4. Materials and Methods: Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis. Results: Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes. Conclusion: PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.

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“…The SVFs were cultured in DMEM (catalog #12800082; Thermo Fisher Scientific) with 10% FBS (catalog #10270; Thermo Fisher Scientific) and 1% penicillinstreptomycin (catalog #15140122; Thermo Fisher Scientific) until 100% confluence. Differentiation of white and brown adipocytes from SVFs was described as we previously reported (21). To collect conditional medium from mature adipocytes, mature adipocytes after 7-day differentiation were washed with PBS three times and cultured in DMEM containing 10% FBS for 24 h. The conditional medium was collected and mixed with the adipocyte differentiation medium in a ratio of 50:50.…”

Section: Isolation Of Mature Adipocytes and Differentiation Of The Stmentioning

confidence: 99%

The Dysfunctional MDM2–p53 Axis in Adipocytes Contributes to Aging-Related Metabolic Complications by Induction of Lipodystrophy

et al. 2018

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Profound loss and senescence of adipose tissues are hallmarks of advanced age, but the underlying cause and their metabolic consequences remain obscure. Proper function of the murine double minute 2 (MDM2)-p53 axis is known to prevent tumorigenesis and several metabolic diseases, yet its role in regulation of adipose tissue aging is still poorly understood. In this study, we show that the proximal p53 inhibitor MDM2 is markedly downregulated in subcutaneous white and brown adipose tissues of mice during aging. Genetic disruption of MDM2 in adipocytes triggers canonical p53-mediated apoptotic and senescent programs, leading to age-dependent lipodystrophy and its associated metabolic disorders, including type 2 diabetes, nonalcoholic fatty liver disease, hyperlipidemia, and energy imbalance. Surprisingly, this lipodystrophy mouse model also displays premature loss of physiological integrity, including impaired exercise capacity, multiple organ senescence, and shorter life span. Transplantation of subcutaneous fat rejuvenates the metabolic health of this aging-like lipodystrophy mouse model. Furthermore, senescence-associated secretory factors from MDM2-null adipocytes impede adipocyte progenitor differentiation via a non-cell-autonomous manner. Our findings suggest that tight regulation of the MDM2-p53 axis in adipocytes is required for adipose tissue dynamics and metabolic health during the aging process.

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A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

Cited by 81 publications

References 72 publications

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

The Dysfunctional MDM2–p53 Axis in Adipocytes Contributes to Aging-Related Metabolic Complications by Induction of Lipodystrophy

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