Role of small proliferative adipocytes: possible beige cell progenitors

Taguchi, Katsuhisa; Kajita, Kazuo; Kitada, Yoshihiko; Fuwa, Masayuki; Asano, Motochika; Ikeda, Takahide; Kajita, Toshiko; Ishizuka, Tatsuo; Kojima, Itaru; Morita, Hiroyuki

doi:10.1530/joe-19-0503

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…Lep , Fabp4 , Plin2 , Adipoq , Gpd1 , Slc2a4 and Pparg are associated with white adipocyte maturation 110 . Plf is expressed by small proliferating preadipocytes with a strong potential to develop into beige adipocytes 111 . ( D ) Expression levels of beige adipocyte genes and Fasn (encoding fatty acid synthase) in P6 and P56 adipocytes.…”

Section: Extended Datamentioning

confidence: 99%

Mitochondrial RNA stimulates beige adipocyte development in young mice

et al. 2022

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Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity.

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Section: Extended Datamentioning

confidence: 99%

Mitochondrial RNA stimulates beige adipocyte development in young mice

et al. 2022

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“…WT1 (Wilms tumor protein 1) plays multiple roles in development, tissue homeostasis and disease ( Hastie, 2017 ). It is also a marker gene of visceral adipocyte precursor, which expressed in small proliferative adipocytes (SPA) isolated from epididymal SPA, but not inguinal SPA ( Taguchi et al, 2020 ). During the late period of mouse gestation, most visceral white adipose tissue (WAT) but no subcutaneous WAT arises from cells expressing Wt1 ( Chau and Hastie, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

et al. 2022

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Background: Fat is a tissue that not just stores energy and plays a protective role; it is also a vital endocrine organ that generates and integrates signals to influence metabolism. Meanwhile, the excessive accumulation of lipids in adipose tissue can lead to metabolic disturbance and diseases. To date, the complicated molecular mechanisms of bovine adipose tissue are still unknown. This study aimed to identify key genes and functionally enriched pathways in various adipose tissue types.Results: The RNAseq data of 264 samples were downloaded from Gene Expression Omnibus (GEO) and analyzed by weighted gene co-expression network analysis (WGCNA). We identified 19 modules that significantly associated with at least one adipose tissue type. The brown module from GSE39618 was most closely associated with intramuscular fat tissue, which contained 550 genes. These genes were significantly enriched in pathways that related to inflammation and disease, such as TNF signaling pathway, IL-17 signaling pathway, and NF-kappa B signaling pathway. The pink module (GSE39618) that contained 58 genes was most closely associated with omental fat tissue. The turquoise (GSE39618), blue (GSE116775), and yellow (GSE65125) module were most closely associated with subcutaneous fat tissue. Genes in these modules were significantly enriched in pathways related to fat metabolism, such as the PPAR signaling pathway, fatty acid metabolism and PI3K-Akt signaling pathway. At last, key genes for intramuscular fat (PTGS2 and IL6), omental fat (ARHGEF5 and WT1), and subcutaneous fat (KIT, QR6Q1, PKD2L1, etc.) were obtained and verified. In addition, it was found that IL10 and VCAM1 might be potential genes to distinguish adipose and muscle.Conclusion: The study applied WGCNA to generate a landscape of adipose tissue and provide a basis for identifying potential pathways and hub genes of different adipose tissue types.

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“…GABRG2 encodes a receptor for the neurotransmitter GABA, which has been detected, along with several other GABA receptors, in mouse brown adipose tissue ( Ikegami et al, 2018 ). GABRG2 is also highly expressed in small proliferating adipocytes of mice, which were suggested to be potential beige adipocyte progenitors ( Taguchi et al, 2020 ). ADRB1 encodes the beta-adrenergic receptor for catecholamines, which stimulate lipolysis and induce adipocyte browning and thermogenesis ( Collins, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal

et al. 2022

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Blubber is a modified subcutaneous adipose tissue in marine mammals that provides energy storage, thermoregulation, hydrodynamic locomotion, and buoyancy. Blubber displays vertical stratification by lipid content, fatty acid composition, and vascularization, leading to the assumption that deeper blubber layers are metabolically active, while superficial layers are mainly structural and thermoregulatory. However, few studies have examined functional stratification of marine mammal blubber directly, especially in pinnipeds. We characterized morphological and transcriptional differences across blubber layers in the northern elephant seal, a deep-diving and fasting-adapted phocid. We collected blubber from seals early in their fasting period and divided blubber cores into three similarly sized portions. We hypothesized that the innermost blubber portion would have higher 1) heterogeneity in adipocyte size, 2) microvascular density, and 3) expression of genes associated with metabolism and hormone signaling than outer blubber. We found that adipocyte area and variance increased from outermost (skin-adjacent) to innermost (muscle-adjacent) blubber layers, suggesting that inner blubber has a higher capacity for lipid storage and turnover than outer blubber. Inner blubber had a higher proportion of CD144+ endothelial cells, suggesting higher microvascular density. In contrast, outer blubber had a higher proportion of CD4+ immune cells than inner blubber, suggesting higher capacity for response to tissue injury. Transcriptome analysis identified 61 genes that were differentially expressed between inner and outer blubber layers, many of which have not been studied previously in marine mammals. Based on known functions of these genes in other mammals, we suggest that inner blubber has potentially higher 1) adipogenic capacity, 2) cellular diversity, and 3) metabolic and neuroendocrine signaling activity, while outer blubber may have higher 1) extracellular matrix synthesis activity and 2) responsiveness to pathogens and cell stressors. We further characterized expression of nine genes of interest identified by transcriptomics and two adipokines with higher precision across blubber layers using targeted assays. Our study provides functional insights into stratification of blubber in marine mammals and a molecular key, including CD144, CD4, HMGCS2, GABRG2, HCAR2, and COL1A2, for distinguishing blubber layers for physiological and functional studies in seals.

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Role of small proliferative adipocytes: possible beige cell progenitors

Cited by 5 publications

References 24 publications

Mitochondrial RNA stimulates beige adipocyte development in young mice

Mitochondrial RNA stimulates beige adipocyte development in young mice

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal

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