Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion

Álvarez-Guaita, Anna; Patel, Satish; Lim, Koini; Haider, Afreen; Liu, Dong; Conway, Olivia J.; K.L., Marcella; Chiarugi, Davide; Saudek, Vladimı́r; O’Rahilly, Stephen; Savage, David B.

doi:10.1016/j.celrep.2021.108810

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…Five genes are transmembrane proteins, including ADIG, GIPR, SLC2A4, HCAR1 , and LHCGR . ADIG is an adipocyte specific transmembrane protein, which was critical for adipogenesis in vivo and in vitro , and ADIG knockout mice were leaner than those in control group fed a high-fat diet ( 29 ). Besides, the variations in ADIG were found to be associated with body mass index (BMI) and leptin levels ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Screening of Bovine Tissue-Specific Expressed Genes and Identification of Genetic Variation Within an Adipose Tissue-Specific lncRNA Gene

Zhang

Jiang

et al. 2022

Front. Vet. Sci.

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Global classification of bovine genes is important for studies of biology and tissue-specific gene editing. Herein, we classified the tissue-specific expressed genes and uncovered an important variation in the promoter region of an adipose tissue-specific lncRNA gene. Statistical analysis demonstrated that the number of genes specifically expressed in the brain was the highest, while it was lowest in the adipose tissues. A total of 1,575 genes were found to be significantly higher expressed in adipose tissues. Bioinformatic analysis and qRT-PCR were used to uncover the expression profiles of the 23 adipose tissue-specific and highly expressed genes in 8 tissues. The results showed that most of the 23 genes have higher expression level in adipose tissue. Besides, we detected a 12 bp insertion/deletion (indel) variation (rs720343880) in the promoter region of an adipose tissue-specific lncRNA gene (LOC100847835). The different genotypes of this variation were associated with carcass traits of cattle. Therefore, the outcomes of the present study can be used as a starting point to explore the development of cattle organs and tissues, as well as to improve the quality of cattle products.

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Section: Discussionmentioning

confidence: 99%

Screening of Bovine Tissue-Specific Expressed Genes and Identification of Genetic Variation Within an Adipose Tissue-Specific lncRNA Gene

Zhang

Jiang

et al. 2022

Front. Vet. Sci.

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“…Adig, as an adipocyte-enriched transmembrane protein, is essential for adipogenesis ( Kim et al, 2005 ). The deficiency of Adig-reduced plasma leptin levels regulated by fat mass and exposed an impairment of leptin secretion from adipose explants ( Alvarez-Guaita et al, 2021 ). Fabp3 is reported to promote adipogenesis and inhibit osteogenesis of BMSCs.…”

Section: Discussionmentioning

confidence: 99%

Expression Profile Analysis of Long Non-coding RNA in OVX Models-Derived BMSCs for Postmenopausal Osteoporosis by RNA Sequencing and Bioinformatics

Huang

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength, and microstructure. Long non-coding RNAs (lncRNAs) are longer than 200 nt, and their functions in osteoporosis is yet not completely understood. We first harvested the bone marrow mesenchymal stem cells (BMSCs) from ovariectomy (OVX) and sham mice. Then, we systematically analyzed the differential expressions of lncRNAs and messenger RNAs (mRNAs) and constructed lncRNA–mRNA coexpression network in order to identify the function of lncRNA in osteoporosis. Totally, we screened 743 lncRNAs (461 upregulated lncRNAs and 282 downregulated lncRNAs) and 240 mRNAs (128 upregulated and 112 downregulated) with significantly differential expressions in OP compared to normal. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses to investigate the functions and pathways of the differential expression of messenger RNAs (mRNAs), a coexpressed network of lncRNA/mRNA. Quantitative PCR (qPCR) validated that the expressions of NONMMUT096150.1, NONMMUT083450.1, and NONMMUT029743.2 were all downregulated, whereas NONMMUT026970.2, NONMMUT051734.2, NONMMUT003617.2, and NONMMUT034049.2 were all upregulated in the OVX group. NONMMUT096150.1, as a key lncRNA in OP, was identified to modulate the adipogenesis of BMSCs. Further analysis suggested that NONMMUT096150.1 might modulate the adipogenesis of BMSCs via the peroxisome proliferator-activated receptor (PPAR) signaling pathway, AMPK signaling pathway, and the lipolysis regulation in adipocyte and adipocytokine signaling pathway. Our study expands the understanding of lncRNA in the pathogenesis of OP.

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“…Leptin secretion is increased by insulin stimulation 19 but this effect is modest compared to the overall circulating levels. Adipose depots that secrete higher leptin have increased LEP mRNA and, at least in vitro , LEP mRNA increases in response to insulin stimulation 20 .…”

Section: Introductionmentioning

confidence: 99%

A mouse model of human mitofusin 2-related lipodystrophy exhibits adipose-specific mitochondrial stress and reduced leptin secretion

Mann

Duan

Álvarez-Guaita

et al. 2022

Preprint

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Mitochondrial dysfunction has been reported in obesity and insulin resistance, but primary genetic mitochondrial dysfunction is generally not associated with these, arguing against a straightforward causal relationship. A rare exception, recently identified in humans, is a syndrome of lower body adipose loss, leptin-deficient severe upper body adipose overgrowth, and insulin resistance caused by the p.Arg707Trp mutation in MFN2, encoding mitofusin-2. How this selective perturbation of mitochondrial function leads to tissue- and adipose depot-specific growth abnormalities and systemic biochemical perturbation is unknown. To address this, Mfn2R707W/R707W knock-in mice were generated and phenotyped on chow and high fat diets. Electron microscopy revealed adipose-specific mitochondrial morphological abnormalities. Oxidative phosphorylation by isolated mitochondria was unperturbed, but the cellular integrated stress response was activated in adipose tissue. Fat mass and distribution, body weight, and systemic glucose and lipid metabolism were unchanged, however serum leptin and adiponectin concentrations, and their secretion from adipose explants were reduced. Pharmacological induction of the integrated stress response in wild-type adipocytes also reduced secretion of leptin and adiponectin, suggesting an explanation for the in vivo findings. These data suggest that the p.Arg707Trp MFN2 mutation perturbs mitochondrial morphology and activates the integrated stress response selectively in adipose tissue. In mice, this does not disrupt most adipocyte functions or systemic metabolism, whereas in humans it is associated with pathological adipose remodelling and metabolic disease. In both species, disproportionate effects on leptin secretion may relate to cell autonomous induction of the integrated stress response.

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Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion

Cited by 11 publications

References 24 publications

Screening of Bovine Tissue-Specific Expressed Genes and Identification of Genetic Variation Within an Adipose Tissue-Specific lncRNA Gene

Screening of Bovine Tissue-Specific Expressed Genes and Identification of Genetic Variation Within an Adipose Tissue-Specific lncRNA Gene

Expression Profile Analysis of Long Non-coding RNA in OVX Models-Derived BMSCs for Postmenopausal Osteoporosis by RNA Sequencing and Bioinformatics

A mouse model of human mitofusin 2-related lipodystrophy exhibits adipose-specific mitochondrial stress and reduced leptin secretion

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