An indispensable role for dynamin-related protein 1 in beige and brown adipogenesis

Mooli, Raja Gopal Reddy; Mukhi, Dhanunjay; Chen, Zhonghe; Buckner, Nia; Ramakrishnan, S

doi:10.1242/jcs.247593

Cited by 10 publications

(4 citation statements)

References 47 publications

(51 reference statements)

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“…Proper mitochondrial dynamics are critical for adipocyte thermogenesis and it was found that the mitochondrial fission protein dynamin-related protein 1 (DRP1) is highly expressed in the BAT and increases with the differentiation of the brown adipocyte. The inhibition of DRP1 expression attenuates mitochondrial biogenesis in beige adipocytes, which confirms that DRP1 plays an important role in beige and brown adipogenesis and thermogenesis 86 .…”

Section: Regulates Adipose Tissue Thermogenesis and Energy Metabolism...supporting

confidence: 59%

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

Wang¹,

Qiu²,

Gan³

et al. 2022

Int. J. Biol. Sci.

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The function of the adipose tissue is influenced by complex interactions between genetics, epigenetics, and the environment, and its dysfunction can cause a variety of metabolic diseases, such as obesity or type 2 diabetes (T2D). The beige/brown adipose tissue plays a crucial role in regulating glucose and lipid metabolism by increasing energy metabolism to generate heat. The adipose tissue thermogenic program is a complex network that involves many signaling pathways regulated by coding RNAs (cRNAs) that encode transcription factor, and non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). This article discusses factors that regulate adipose tissue thermogenesis, including cRNAs and ncRNAs, and the important role of thermogenic adipose tissue in obesity-related metabolic syndrome. Several studies have shown that some cRNAs and ncRNAs can modulate the thermogenic function of adipose tissue in different ways. This article reviews the roles of cRNAs and ncRNAs in regulating thermogenesis in the beige/brown adipose tissue and the important role of the beige/brown adipose tissue in maintaining the balance of glucose and lipid metabolism in the body.

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Section: Regulates Adipose Tissue Thermogenesis and Energy Metabolism...supporting

confidence: 59%

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

Wang¹,

Qiu²,

Gan³

et al. 2022

Int. J. Biol. Sci.

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“…Furthermore, DNM1 is overexpressed in brown adipose tissue, and its level escalates during beige and brown adipocyte differentiation. Inhibition of DNM1 expression was confirmed to mitigate beige adipocyte differentiation, thereby validating its essential role in beige and brown adipogenesis ( Mooli et al, 2020 ).…”

Section: Discussionmentioning

confidence: 76%

Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs

Chen,

Ren,

et al. 2023

Front. Genet.

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Fat deposition is an economically important trait in pigs. Ningxiang pig, one of the four famous indigenous breeds in China, is characterized by high fat content. The underlying gene expression pattern in different developmental periods of backfat tissue remains unclear, and the purpose of this investigation is to explore the potential molecular regulators of backfat tissue development in Ningxiang pigs. Backfat tissue (three samples for each stage) was initially collected from different developmental stages (60, 120, 180, 240, 300, and 360 days after birth), and histological analysis and RNA sequencing (RNA-seq) were then conducted. Fragments per kilobase of transcript per million (FPKM) method was used to qualify gene expressions, and differentially expressed genes (DEGs) were identified. Furthermore, strongly co-expressed genes in modules, which were named by color, were clustered by Weighted gene co-expression network analysis (WGCNA) based on dynamic tree cutting algorithm. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment were subsequently implemented, and hub genes were described in each module. Finally, QPCR analysis was employed to validate RNA-seq data. The results showed that adipocyte area increased and adipocyte number decreased with development of backfat tissue. A total of 1,024 DEGs were identified in five comparison groups (120 days vs. 60 days, 180 days vs. 120 days, 240 days vs. 180 days, 300 days vs. 240 days, and 360 days vs. 300 days). The turquoise, red, pink, paleturquoise, darkorange, and darkgreen module had the highest correlation coefficient with 60, 120, 180, 240, 300, and 360 days developmental stage, while the tan, black and turquoise module had strong relationship with backfat thickness, adipocyte area, and adipocyte number, respectively. Thirteen hub genes (ACSL1, ACOX1, FN1, DCN, CHST13, COL1A1, COL1A2, COL6A3, COL5A1, COL14A1, OAZ3, DNM1, and SELP) were recognized. ACSL1 and ACOX1 might perform function in the early developmental stage of backfat tissue (60 days), and FN1, DCN, COL1A1, COL1A2, COL5A1, COL6A3, and COL14A1 have unignorable position in backfat tissue around 120 days developmental stage. Besides, hub genes SELP and DNM1 in modules significantly associated with backfat thickness and adipocyte area might be involved in the process of backfat tissue development. These findings contribute to understand the integrated mechanism underlying backfat tissue development and promote the progress of genetic improvement in Ningxiang pigs.

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“…Although there was no change in mitochondrial DNA and PGC1α, the UCP1 levels were decreased and the DRP1 levels were increased in mice fed with a HFD. This suggested that it was a strong indicator of change from white adipose tissue to brown adipose tissue (i.e., UCP1 levels) and fission of mitochondria (i.e., DRP1 levels) (Shimokawa et al, 2019;Mooli et al, 2020). Interestingly, the treatment with PB mitigated mitochondrial fission and promoted browning of the white adipose tissue (Figure 4C).…”

Section: Resultsmentioning

confidence: 93%

Epigenetics, 1-Carbon Metabolism, and Homocysteine During Dysbiosis

et al. 2021

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Although a high-fat diet (HFD) induces gut dysbiosis and cardiovascular system remodeling, the precise mechanism is unclear. We hypothesize that HFD instigates dysbiosis and cardiac muscle remodeling by inducing matrix metalloproteinases (MMPs), which leads to an increase in white adipose tissue, and treatment with lactobacillus (a ketone body donor from lactate; the substrate for the mitochondria) reverses dysbiosis-induced cardiac injury, in part, by increasing lipolysis (PGC-1α, and UCP1) and adipose tissue browning and decreasing lipogenesis. To test this hypothesis, we used wild type (WT) mice fed with HFD for 16 weeks with/without a probiotic (PB) in water. Cardiac injury was measured by CKMB activity which was found to be robust in HFD-fed mice. Interestingly, CKMB activity was normalized post PB treatment. Levels of free fatty acids (FFAs) and methylation were increased but butyrate was decreased in HFD mice, suggesting an epigenetically governed 1-carbon metabolism along with dysbiosis. Levels of PGC-1α and UCP1 were measured by Western blot analysis, and MMP activity was scored via zymography. Collagen histology was also performed. Contraction of the isolated myocytes was measured employing the ion-optic system, and functions of the heart were estimated by echocardiography. Our results suggest that mice on HFD gained weight and exhibited an increase in blood pressure. These effects were normalized by PB. Levels of fibrosis and MMP-2 activity were robust in HFD mice, and treatment with PB mitigated the fibrosis. Myocyte calcium-dependent contraction was disrupted by HFD, and treatment with PB could restore its function. We conclude that HFD induces dysbiosis, and treatment with PB creates eubiosis and browning of the adipose tissue.

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An indispensable role for dynamin-related protein 1 in beige and brown adipogenesis

Cited by 10 publications

References 47 publications

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs

Epigenetics, 1-Carbon Metabolism, and Homocysteine During Dysbiosis

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