L2Δ13, a splicing isoform of lysyl oxidase-like 2, causes adipose tissue loss via the gut microbiota and lipid metabolism
Yang Chen,
Li-Xia He,
Jin-Ling Chen,
Xin Xu,
Juan-Juan Wang,
Xiu-Hui Zhan,
Ji-Wei Jiao,
Geng Dong,
En-Min Li,
Li-Yan Xu
Affiliations
Yang Chen
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Li-Xia He
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Jin-Ling Chen
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Xin Xu
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Juan-Juan Wang
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Xiu-Hui Zhan
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Ji-Wei Jiao
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
Geng Dong
Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Medical Informatics Research Center, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
En-Min Li
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Corresponding author
Li-Yan Xu
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China; Corresponding author
Summary: Obesity is primarily characterized by the dysregulation of lipid metabolism and gut microbiota. Here, we found that the body weight of transgenic mice overexpressing L2Δ13, a selectively spliced isoform of lysyl oxidase-like 2 (LOXL2), was lower than that of wild-type (WT) mice. Numerous microbiotas were significantly changed and most microbial metabolites were abnormal in L2Δ13 mice. Lipid metabolites in feces were negatively correlated with those in plasma, suggesting that L2Δ13 may affect lipid uptake, and potentially, adipose tissue homeostasis. This was supported by the weight loss and decreased area of adipose tissue in L2Δ13 mice. Adipogenic differentiation of primary stromal vascular fraction cells showed that the lipid droplets of L2Δ13 cells were significantly smaller than those of WT cells. Adipocyte differentiation-associated genes were also downregulated in adipose tissue from L2Δ13 mice. Thus, L2Δ13 can induce adipose tissue loss in mice by affecting gut microbiota homeostasis and multi-tissue lipid metabolism.
