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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: Recently, we have synthesized several boron-containing small molecules.Among these novel compounds, BF175 can specifically block the binding of MED15-KIX to SREBP1a-TAD in vitro, resulting in an inhibition of the SREBP transcriptional activity and a decrease of SREBP target gene expression in cultured hepatocytes.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: Recently, we have synthesized several boron-containing small molecules.Among these novel compounds, BF175 can specifically block the binding of MED15-KIX to SREBP1a-TAD in vitro, resulting in an inhibition of the SREBP transcriptional activity and a decrease of SREBP target gene expression in cultured hepatocytes.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