microRNAs as Possible Targets for Obesity Treatment

Researchers use widefield microscopy to image adipose and brain tissue as part of their work to find new ways to treat obesity.

Obesity refers to the excessive amount of body fat, often as a result from eating more calories (energy) than are used. This can be a serious medical issue with increased risk of health problems including heart disease, diabetes, high blood pressure and certain cancers.

Dr. Koh Ono and Dr. Takahiro Horie are cardiologists at Kyoto University Hospital (Japan). They provide medical care in the field of cardiovascular medicine as well as conduct basic research in the Department of Cardiovascular Medicine at Kyoto University Graduate School of Medicine.

Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University (Japan)
Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University (Japan)

Their research interests lie in elucidating the molecular mechanisms of cardiovascular diseases such as atherosclerosis, heart failure, dyslipidemia, insulin resistance and obesity.

They focus on non-coding RNAs, especially microRNAs.

They are also focused on establishing new therapeutic methods for these diseases and already have four patents on therapeutic methods.

Dr. Ono and Dr. Horie recently published an article using wide field microscopy to investigate a specific microRNA (miR-33) as a potential target for obesity treatment. They provided some insights on their recent work.

Representative images of HE staining for the BAT of miR-33f/f and miR-33f/f DBH-Cre mice kept at 4 °C for 5 h. Scale bar, 200 microns. Image courtesy of Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University (Japan)

Representative widefield microscopy images of HE staining for the brown adipose tissue (BAT) of miR-33f/f and miR-33f/f DBH-Cre mice kept at 4°C for 5h. Scalebar: 200μm. There are many more lipid droplets in miR-33f/f DBH-Cre mice after cold treatment.

Tell us about your recent publication.

We have been investigating the functions of microRNAs in cardiovascular diseases. We found that micoRNA-33 (miR-33), located in the intron of SREBF2, plays an important role in lipid metabolism. miR-33-deficient mice showed increased serum HDL-C (good cholesterol) and decreased atherosclerosis and abdominal aortic aneurysm formation.

Representative images of HE staining for inguinal WAT kept at 16°C for 1 week in miR-33f/f and miR-33f/fDBH-Cre mice. Scalebar: 200μm. Image courtesy of Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University, Japan

Representative images of HE staining for inguinal white adipose tissue (WAT) kept at 16°C for 1 week in miR-33f/f and miR-33f/f DBH-Cre mice. Scalebar: 200μm. Beige or brite (brown-in-white) adipocytes are present in WAT and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis.

However, these mice showed an obese phenotype when fed a high-fat diet. In this paper, we show that miRNA-33 in the brain is essential for adaptive thermogenesis. Adaptive thermogenesis is the process by which animals produce heat in response to cold environments and is essential for survival. Heat is produced in brown adipose tissue (BAT) and lipids are used as fuel. We found that miRNA-33 maintains adaptive heat production in BAT by targeting GABAA receptor subunits in the brain to suppress GABAergic inhibitory signals and increase sympathetic tone. Therefore, miR-33 in the brain may be an important regulator of systemic metabolism.

Representative images of c-fos immunohistochemistry in the rRPa of miR-33+/+ and miR-33−/− mice kept at 4°C for 2h. Scalebar:100μm. Image courtesy of Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University (Japan)

Representative images of c-fos immunohistochemistry in the rostral raphe pallidus nucleus (rRPa) of the medulla of miR-33+/+ and miR-33−/−  mice kept at 4°C for 2h. Scalebar: 100μm. The number of c-fos-positive cells can be used as an indicator of neuronal activation.

How did you use wide field microscopy in your publication?

We used microscopy to visualize brown adipose tissues (BAT) and brain sections with HE staining and immunohistochemical staining. We also took fluorescent pictures of brains infected with AAV9 vector and expressing shRNA with this AAV9 vector. The data were acquired with ZEISS Axio Observer 7 and ZEISS ZEN software. This system was easy to use and the data were easy to analyze. With this system, it was possible to easily observe the microstructure of BAT, brain activation by cold stimulation and infection efficiency of AAV9 vectors.

Representative fluorescent images of the region around the 3rd ventricle of miR-33f/fDBH-Cre mice brains infected with AAV9 vector. Scalebar: 100μm. Image courtesy of Dr. Koh Ono and Dr. Takahiro Horie, Kyoto University (Japan)

Representative fluorescent images of the region around the 3rd ventricle of miR-33f/f DBH-Cre mice brains infected with AAV9 vector. Scalebar: 100μm.

Learn more

Read the full article: microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity Link

Learn more about ZEISS solutions for widefield microscopy.

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