4.5 Article

MiR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 479, Issue -, Pages 110-116

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2018.09.007

Keywords

MiR-107; Notch; CDK6; Adipogenesis; Triglyceride; Adipocyte

Funding

  1. Finnish Diabetes Research Foundation
  2. Liv och Halsa Foundation
  3. Finnish Foundation for Cardiovascular Research
  4. Sigrid Juselius Foundation
  5. Baden-Wurttemberg Stiftung

Ask authors/readers for more resources

MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Review Pharmacology & Pharmacy

The emerging roles of OSBP-related proteins in cancer: Impacts through phosphoinositide metabolism and protein-protein interactions

Vesa M. Olkkonen

Summary: Oxysterol-binding protein-related proteins (ORPs) are a family of intracellular lipid binding/transfer proteins involved in lipid transport within cells. They have the ability to bind phosphatidylinositol polyphosphates (PIPs). Dysregulation of certain ORP family members, such as ORP3, -4, -5, and -8, is implicated in cancer growth through their effects on signaling events, protein interactions, and cellular lipid transport. This review discusses the functional evidence of ORPs in cancer growth and explores the potential of targeting ORPs for anti-cancer therapy.

BIOCHEMICAL PHARMACOLOGY (2022)

Article Medicine, Research & Experimental

Compound heterozygous variants in OTULIN are associated with fulminant atypical late-onset ORAS

Julia Zinngrebe, Barbara Moepps, Thomas Monecke, Peter Gierschik, Ferdinand Schlichtig, Thomas F. E. Barth, Gudrun Strauss, Elena Boldrin, Carsten Posovszky, Ansgar Schulz, Ortraud Beringer, Eva Rieser, Eva-Maria Jacobsen, Myriam Ricarda Lorenz, Klaus Schwarz, Ulrich Pannicke, Henning Walczak, Dierk Niessing, Catharina Schuetz, Pamela Fischer-Posovszky, Klaus-Michael Debatin

Summary: This article describes an atypical clinical manifestation of OTULIN-related autoinflammatory syndrome (ORAS) caused by new compound heterozygous variants (c.258G>A (p.M86I)/c.500G>C (p.W167S)) in the OTULIN gene. The study found that these variants compromised the binding of OTULIN to linear ubiquitin, leading to the development of the disease.

EMBO MOLECULAR MEDICINE (2022)

Review Biochemistry & Molecular Biology

Cholesterol transport in the late endocytic pathway: Roles of ORP family proteins

Vesa M. Olkkonen, Elina Ikonen

Summary: This review summarizes the role of OSBP family members in facilitating cholesterol trafficking within the endocytic pathway, particularly at membrane contact sites within the cell. ORP1 isoforms have been shown to mediate cholesterol transport between the endoplasmic reticulum and late endosomes/lysosomes, while ORP2 plays a role in transferring cholesterol between late endosomes and recycling endosomes. These processes involve lipid exchange and contribute to regulating cellular signaling pathways.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes

Maria A. Ahonen, Marcus Horing, Van Dien Nguyen, Sami Qadri, Juuso H. Taskinen, Meghana Nagaraj, Martin Wabitsch, Pamela Fischer-Posovszky, You Zhou, Gerhard Liebisch, P. A. Nidhina Haridas, Hannele Yki-Jarvinen, Vesa M. Olkkonen

Summary: This study found that thyroid hormone responsive protein (THRSP) is regulated by insulin in human adipose tissue and adipocytes. Insulin resistance leads to downregulation of THRSP expression. Silencing of THRSP results in impaired mitochondrial function and disrupted lipid metabolism.

MOLECULAR MEDICINE (2022)

Review Endocrinology & Metabolism

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Anke Hinney, Antje Koerner, Pamela Fischer-Posovszky

Summary: Obesity is a complex and multifactorial disease that starts in early childhood and has lifelong consequences. It is influenced by both genetic predisposition and environmental factors. While polygenic obesity is common and has small effects, rare monogenic obesity syndromes are caused by specific pathogenic variants in a single gene with large effects. These genes are mainly involved in the central nervous regulation of body weight, such as the leptin-melanocortin pathway. Genetic testing is recommended for patients with rapid weight gain in infancy and other clinical suggestive features, as novel pharmacological treatments targeting the central melanocortin pathway are emerging. Early identification of syndromic obesity patients can lead to appropriate treatment, preventing obesity-related complications and stigma.

NATURE REVIEWS ENDOCRINOLOGY (2022)

Review Endocrinology & Metabolism

20 Years with SGBS cells-a versatile in vitro model of human adipocyte biology

Daniel Tews, Rolf E. Brenner, Reiner Siebert, Klaus-Michael Debatin, Pamela Fischer-Posovszky, Martin Wabitsch

Summary: SGBS cells, derived from adipose tissue, are widely used as a cell model for studying human adipogenesis and adipocyte biology. These cells can proliferate and differentiate into adipocytes for over 50 population doublings, providing an almost unlimited source of adipocyte progenitor cells. Research using SGBS cells has resulted in numerous publications covering various aspects of adipogenesis and adipocyte biology.

INTERNATIONAL JOURNAL OF OBESITY (2022)

Editorial Material Endocrinology & Metabolism

AcroBATics: how dying brown adipocytes trigger browning

Julia Zinngrebe, Pamela Fischer-Posovszky

Summary: Inosine, released from apoptotic brown adipocytes, has been identified as an inducer of thermogenic adipose tissue, uncovering a novel mechanism of adipose tissue plasticity.

NATURE REVIEWS ENDOCRINOLOGY (2022)

Article Multidisciplinary Sciences

Prevalence estimates of putatively pathogenic leptin variants in the gnomAD database

Luisa Sophie Rajcsanyi, Yiran Zheng, Pamela Fischer-Posovszky, Martin Wabitsch, Johannes Hebebrand, Anke Hinney

Summary: Homozygosity for pathogenic variants in the leptin gene leads to severe early-onset obesity. The prevalence of these variants in the general population is low, with variations among different populations.

PLOS ONE (2022)

Article Biochemistry & Molecular Biology

Global effects of pharmacologic inhibition of OSBP in human umbilical vein endothelial cells

Juuso H. Taskinen, Hanna Ruhanen, Silke Matysik, Reijo Kakela, Vesa M. Olkkonen

Summary: This study elucidated the effects of inhibiting OSBP on endothelial cells, including changes in the lipidome, transcriptome, and disruption of in vitro angiogenic capacity. Thus, OSBP plays a crucial regulatory role in endothelial cell lipid homeostasis and angiogenic capacity.

STEROIDS (2022)

Meeting Abstract Hematology

Venetoclax Resistance in B-Cell Precursor Acute Lymphoblastic Leukemia Is Characterized By Increased Mitochondrial Metabolism and Can be Overcome By Co-Targeting Oxidative Phosphorylation

Alexandra Niedermayer, Stefanie Enzenmueller, Felix Seyfried, Daniel Tews, Pamela Fischer-Posovszky, Ulrich Rupp, Paul Walther, Klaus-Michael Debatin, Luder Hinrich Meyer

BLOOD (2022)

Article Biochemistry & Molecular Biology

Cholesterol transfer via endoplasmic reticulum contacts mediates lysosome damage repair

Maja Radulovic, Eva Maria Wenzel, Sania Gilani, Lya K. K. Holland, Alf Hakon Lystad, Santosh Phuyal, Vesa M. Olkkonen, Andreas Brech, Marja Jaattela, Kenji Maeda, Camilla Raiborg, Harald Stenmark

Summary: This study reveals an additional mechanism for lysosome repair that is activated independently of the ESCRT machinery. It shows that damaged lysosomes rapidly form contacts with the endoplasmic reticulum (ER), mediated by ER proteins VAPA/B, which provide lipids for membrane repair. The study also highlights the importance of lysosomal phosphatidylserine and cholesterol accumulation, as well as the generation and removal of PtdIns4P in this repair response.

EMBO JOURNAL (2022)

Article Biochemistry & Molecular Biology

Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies

Lena Molitor, Melina Klostermann, Sabrina Bacher, Juliane Merl-Pham, Nadine Spranger, Sandra Burczyk, Carolin Ketteler, Ejona Rusha, Daniel Tews, Anna Pertek, Marcel Proske, Anke Busch, Sarah Reschke, Regina Feederle, Stefanie M. Hauck, Helmut Blum, Micha Drukker, Pamela Fischer-Posovszky, Julian Koenig, Kathi Zarnack, Dierk Niessing

Summary: The RNA-binding protein PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Reduced levels of PURA affect the formation and composition of P-bodies, leading to dysregulation of RNA processing. This study proposes PURA Syndrome as a new model for studying the connection between P-body-associated RNA regulation and neurodevelopmental disorders.

NUCLEIC ACIDS RESEARCH (2023)

Editorial Material Cell Biology

Energy saver: Monocytes hibernate in bone marrow upon fasting

Jan Tuckermann, Pamela Fischer-Posovszky

Summary: Immune functions are influenced by nutritional state. A recent publication in Immunity by Janssen et al. revealed that fasting-induced glucocorticoid release leads to the movement of monocytes from blood into the bone marrow. Upon refeeding, these chronologically older monocytes are released again and have detrimental effects during bacterial infection.

CELL METABOLISM (2023)

Meeting Abstract Endocrinology & Metabolism

microRNA-27a-a strand specific regulator of adipogenesis and adipocyte function

Julian Roos, Hang Wu, Taner Pula, Daniel Tews, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer-Posovszky

HORMONE RESEARCH IN PAEDIATRICS (2022)

Meeting Abstract Endocrinology & Metabolism

Inhibition of Neuritin 1 induces browning in human white adipocytes and protects from obesity in vivo

Daniel Tews, Julian Roos, Gordon Winter, Ambros Beer, Volker Rasche, Elly Nedivi, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky

HORMONE RESEARCH IN PAEDIATRICS (2022)

Article Cell Biology

Endosomal signaling via cAMP in parathyroid hormone (PTH) type 1 receptor biology

Karina A. Pena, Sofya Savransky, Breanna Lewis

Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia

Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu

Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

Activation of mitophagy improves cognitive dysfunction in diabetic mice with recurrent non-severe hypoglycemia

Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu

Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

17β-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-β/ Smad axis

Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou

Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

Deregulation of ABCG1 early in life contributes to prostate carcinogenesis in maternally malnourished offspring rats

Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin

Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

Transcriptional landscape of human trophoblast cells treated with calcitriol and TGF-131

Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera

Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study

Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban

Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)

Article Cell Biology

Blocking the interaction between circTNRC18 and LIN28A promotes trophoblast epithelial-mesenchymal transformation and alleviates preeclampsia

Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen

Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2024)