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Inhibition of SREBP transcriptional activity by a boron-containing compound improves lipid homeostasis in diet-induced obesity.

Zhao X - Diabetes (2014)

Bottom Line: Previous studies have shown that the conserved transcriptional cofactor Mediator complex is critically required for the SREBP transcriptional activity, and recruitment of the Mediator complex to the SREBP transactivation domains (TADs) is through the MED15-KIX domain.Recently, we have synthesized several boron-containing small molecules.These results suggest that blocking the interaction between SREBP-TADs and the Mediator complex by small molecules may represent a novel approach for treating diseases with aberrant lipid homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NYDepartment of Developmental & Molecular Biology, Albert Einstein College of Medicine, Bronx, NYDepartment of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

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A: Effects of BF175 on lipid accumulation in Drosophila larvae as detected by Oil Red O staining followed by isopropanol extraction. B–E: C57BL/6J mice were first fed with HFD for 4 weeks and then treated with BF175 (0.3 mg/g body weight per week) or buffer (containing 0.5% DMSO) for a total of 7 days by subcutaneously implanted osmotic pumps. All mice were continuously provided with HFD during the treatment. At the end of the treatment, mice were killed and the livers were collected. B: Effects of BF175 on the triglyceride levels in the mouse liver. C and E: Relative mRNA levels of the indicated genes as detected by qRT-PCR in the mouse liver. D: Immunoblots of hepatic SREBP-1 proteins. Three representative mice from each group are shown. Data are the mean ± SD (n = 6). *P < 0.05; #P < 0.01 vs. control (DMSO).
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Figure 5: A: Effects of BF175 on lipid accumulation in Drosophila larvae as detected by Oil Red O staining followed by isopropanol extraction. B–E: C57BL/6J mice were first fed with HFD for 4 weeks and then treated with BF175 (0.3 mg/g body weight per week) or buffer (containing 0.5% DMSO) for a total of 7 days by subcutaneously implanted osmotic pumps. All mice were continuously provided with HFD during the treatment. At the end of the treatment, mice were killed and the livers were collected. B: Effects of BF175 on the triglyceride levels in the mouse liver. C and E: Relative mRNA levels of the indicated genes as detected by qRT-PCR in the mouse liver. D: Immunoblots of hepatic SREBP-1 proteins. Three representative mice from each group are shown. Data are the mean ± SD (n = 6). *P < 0.05; #P < 0.01 vs. control (DMSO).

Mentions: The inhibitory effects of BF175 on SREBP-dependent lipogenic gene expression in cultured hepatocytes prompted us to determine whether BF175 inhibits feeding-induced lipid accumulation in the fat body of Drosophila, because SREBP plays a pivotal and conserved role in the process (19). As shown in Fig. 5A, short-term feeding Drosophila larvae with BF175 significantly decreased lipid levels in the fat body, as quantitatively measured after Oil Red O staining.


Inhibition of SREBP transcriptional activity by a boron-containing compound improves lipid homeostasis in diet-induced obesity.

Zhao X - Diabetes (2014)

A: Effects of BF175 on lipid accumulation in Drosophila larvae as detected by Oil Red O staining followed by isopropanol extraction. B–E: C57BL/6J mice were first fed with HFD for 4 weeks and then treated with BF175 (0.3 mg/g body weight per week) or buffer (containing 0.5% DMSO) for a total of 7 days by subcutaneously implanted osmotic pumps. All mice were continuously provided with HFD during the treatment. At the end of the treatment, mice were killed and the livers were collected. B: Effects of BF175 on the triglyceride levels in the mouse liver. C and E: Relative mRNA levels of the indicated genes as detected by qRT-PCR in the mouse liver. D: Immunoblots of hepatic SREBP-1 proteins. Three representative mice from each group are shown. Data are the mean ± SD (n = 6). *P < 0.05; #P < 0.01 vs. control (DMSO).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4066337&req=5

Figure 5: A: Effects of BF175 on lipid accumulation in Drosophila larvae as detected by Oil Red O staining followed by isopropanol extraction. B–E: C57BL/6J mice were first fed with HFD for 4 weeks and then treated with BF175 (0.3 mg/g body weight per week) or buffer (containing 0.5% DMSO) for a total of 7 days by subcutaneously implanted osmotic pumps. All mice were continuously provided with HFD during the treatment. At the end of the treatment, mice were killed and the livers were collected. B: Effects of BF175 on the triglyceride levels in the mouse liver. C and E: Relative mRNA levels of the indicated genes as detected by qRT-PCR in the mouse liver. D: Immunoblots of hepatic SREBP-1 proteins. Three representative mice from each group are shown. Data are the mean ± SD (n = 6). *P < 0.05; #P < 0.01 vs. control (DMSO).
Mentions: The inhibitory effects of BF175 on SREBP-dependent lipogenic gene expression in cultured hepatocytes prompted us to determine whether BF175 inhibits feeding-induced lipid accumulation in the fat body of Drosophila, because SREBP plays a pivotal and conserved role in the process (19). As shown in Fig. 5A, short-term feeding Drosophila larvae with BF175 significantly decreased lipid levels in the fat body, as quantitatively measured after Oil Red O staining.

Bottom Line: Previous studies have shown that the conserved transcriptional cofactor Mediator complex is critically required for the SREBP transcriptional activity, and recruitment of the Mediator complex to the SREBP transactivation domains (TADs) is through the MED15-KIX domain.Recently, we have synthesized several boron-containing small molecules.These results suggest that blocking the interaction between SREBP-TADs and the Mediator complex by small molecules may represent a novel approach for treating diseases with aberrant lipid homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NYDepartment of Developmental & Molecular Biology, Albert Einstein College of Medicine, Bronx, NYDepartment of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

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Related in: MedlinePlus