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Phenotypic Discovery of SB1501, an Anti‐obesity Agent, through Modulating Mitochondrial Activity
Author(s) -
Jo Ala,
Kim Mingi,
Kim Jong In,
Ha Jaeyoung,
Hwang Yoon Soo,
Nam Hyunsung,
Hwang Injae,
Kim Jae Bum,
Park Seung Bum
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100062
Subject(s) - adipose tissue , mitochondrial biogenesis , white adipose tissue , phenotype , obesity , 3t3 l1 , mitochondrion , biology , adipogenesis , microbiology and biotechnology , biochemistry , chemistry , endocrinology , gene
Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity‐related metabolic disorders are necessary. Here, we aimed to identify new anti‐obesity agents using a phenotype‐based approach. We performed image‐based high‐content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure‐activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3‐L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3‐L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti‐obesity effect of SB1501 may result from perturbation of the PGC‐1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti‐obesity agent via modulating mitochondrial activities.