MafB deficiency accelerates the development of obesity in mice

Tran, Mai; Hamada, Michito; Nakamura, Megumi; Jeon, Hyojung; Kamei, Risa; Tsunakawa, Yuki; Kulathunga, Kaushalya; Lin, Yanfu; Fujisawa, Kumiko; Kudo, Takashi; Takahashi, Satoru

doi:10.1002/2211-5463.12058

Cited by 35 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This discrepancy may reflect the use of mice with different genetic backgrounds in the present study, whereas the difference in the Cre drivers used is unlikely to have contributed, because we also generated a Mafb conditional-knockout mouse with Pdx1-Cre (24), which exhibited the same phenotype as Mafb ⌬Endo mice (data not shown). Indeed, the Mafb f/f mice used in the present study (25,26) and by Conrad et al (10,27) were generated in mouse embryonic stem (ES) cells from different genetic backgrounds, e.g., C57BL/6J and 129S4/SvJae, which may explain the phenotypic variations.…”

Section: Discussionmentioning

confidence: 93%

“…All animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Tsukuba. Endocrine cell-specific and TAM-dependent Mafb knockout mice were generated by crossing Mafb f/f mice (25,26) with either Ngn3-Cre (52) or CAGG-CreER (stock number 004682; The Jackson Laboratory) (53) transgenic mice. Mafb f/f mice were generated in a C57BL/6J strain background, as described previously (25,26).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo

et al. 2018

Self Cite

View full text Add to dashboard Cite

The MafB transcription factor is expressed in pancreatic α and β cells during development but becomes exclusive to α cells in adult rodents. -null ( ) mice were reported to have reduced α- and β-cell numbers throughout embryonic development. To further analyze the postnatal function of MafB in the pancreas, we generated endocrine cell-specific ( ) and tamoxifen-dependent ( ) knockout mice. mice exhibited reduced populations of insulin-positive (insulin) and glucagon cells at postnatal day 0, but the insulin cell population recovered by 8 weeks of age. In contrast, the Arx glucagon cell fraction and glucagon expression remained decreased even in adulthood. mice, with deleted after pancreas maturation, also demonstrated diminished glucagon cells and glucagon content without affecting β cells. A decreased Arx glucagon cell population in mice was compensated for by an increased Arx pancreatic polypeptide cell population. Furthermore, gene expression analyses from both and islets revealed that MafB is a key regulator of glucagon expression in α cells. Finally, both mutants failed to respond to arginine, likely due to impaired arginine transporter gene expression and glucagon production ability. Taken together, our findings reveal that MafB is critical for the functional maintenance of mouse α cells , including glucagon production and secretion, as well as in development.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Under these conditions, the size and weight of white adipose tissue increased, and AIM inhibited fat synthesis after uptake by adipocytes. As a reduction in AIM expression was observed in the adipose tissue macrophages of Mafbdeficient mice, AIM reduction may be the cause of obesity in Mafb-deficient mice [73]. another recent report demonstrated that after inducing ischemic stroke, macrophage-specific Mafb-deficient mice (Mafb f/f ::LysM-Cre) showed excessive inflammation.…”

Section: The Phenotype Of Mafb-deficient Macrophages and Mafb Target mentioning

confidence: 98%

Role of MafB in macrophages

et al. 2020

Self Cite

View full text Add to dashboard Cite

The transcription factor MafB regulates macrophage differentiation. However, studies on the phenotype of Mafb-deficient macrophages are still limited. Recently, it was shown that the specific expression of MafB permits macrophages to be distinguished from dendritic cells. In addition, MafB has been reported to be involved in various diseases related to macrophages. Studies using macrophage-specific Mafb-deficient mice show that MafB is linked to atherosclerosis, autoimmunity, obesity, and ischemic stroke, all of which exhibit macrophage abnormality. Therefore, MafB is hypothesized to be indispensable for the regulation of macrophages to maintain systemic homeostasis and may serve as an innovative target for treating macrophage-related diseases.

show abstract

“…MAFB also links to the metabolism and development of obesity and diabetes. The MAFB-deficient mice exhibited higher body weights and faster rates of body weight increase than control mice [26]. Up-regulation of MAFB expression in human adipocytes is correlated with adverse metabolic features and inflammation which may lead to the development of 10 insulin resistance [27].…”

Section: Supervised Classification Of Genes Expression Discriminate Dmentioning

confidence: 99%

Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

Khoshnejat

Kavousi

Banaei-Moghaddam

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake thus plays a critical role in T2DM. Here, we attempt to provide a better understanding of abnormalities in this tissue. Methods: We have explored the muscle gene expression pattern in healthy and newly-diagnosed T2DM individuals using supervised and unsupervised classification along with the discovery of potential subtypes of type 2 diabetes. Results: A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminates between normoglycemic and diabetic groups. A gene set comprises of 26 genes identified which was able to discriminate healthy from diabetic individuals with the 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct potential subtypes with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion: This study implies that it seems the disease has triggered through different cellular/molecular mechanisms. Therefore, subtyping of T2DM patients in combination with real clinical profiles of patients will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

show abstract

MafB deficiency accelerates the development of obesity in mice

Cited by 35 publications

References 30 publications

MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo

MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo

Role of MafB in macrophages

Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

Contact Info

Product

Resources

About