Only one human fat cell subtype responds to insulin stimulation

Date:
August 10, 2021
Source:
Karolinska Institutet
Summary:
It is well known that fat cells can influence our sensitivity
to insulin.

Now, researchers have discovered that there are three different
subtypes of mature fat cells in white adipose tissue and that it is
only one of these, called AdipoPLIN, that responds to insulin. The
findings may be relevant for future treatments of metabolic diseases
such as Type 2 diabetes.



FULL STORY ==========================================================================
It is well known that fat cells can influence our sensitivity to
insulin. Now, researchers at Karolinska Institutet in Sweden have
discovered that there are three different subtypes of mature fat cells in
white adipose tissue and that it is only one of these, called AdipoPLIN,
that responds to insulin. The findings may be relevant for future
treatments of metabolic diseases such as Type 2 diabetes.


========================================================================== "These findings increase our knowledge about the function of fat tissue,"
says co-corresponding author Niklas Mejhert, researcher at the Department
of Medicine, Huddinge, at Karolinska Institutet. "They show that the
overall capacity of fat tissue to respond to insulin is determined by
the proportion and function of a specific fat cell subtype. This could
have implications for diseases such as obesity, insulin resistance
and Type 2 diabetes." In the study, which is published in the journal
Cell Metabolism, the researchers identified 18 cell classes that forms
clusters in white adipose tissue in humans. Of these, three constituted
mature fat cells with distinct phenotypes.

To test if the fat cell subtypes were linked to any specific function,
the researchers examined in part how these subtypes in four people
reacted to short-term increases in insulin levels. The result showed that insulin activated the gene expression in the subtype AdipoPLIN but did
not materially affect the other two subtypes. Additionally, the response
to insulin stimulation was proportional to the individual's whole-body
insulin sensitivity.

"Our findings challenge the current view of insulin resistance as a
generally reduced response to insulin in the fat cells," says Mikael
Ryde'n, professor in the same department and another of the study's co-corresponding authors.

"Instead, our study suggests that insulin resistance, and possibly
type 2 diabetes, could be due to changes in a specific subtype of fat
cells. This shows that fat tissue is a much more complex tissue than
previously thought.

Like muscle tissue, people have several types of fat cells with different functions, which opens up for future interventions targeted at different
fat cell types." In the study, the Ryde'n and Mejhert group used a
special technique called spatial transcriptomics, which was developed by
among others collaboration partner Patrik Staahl, associate professor at
KTH Royal Institute of Technology and SciLifeLab. Spatial transcriptomics generates information about tissue organization via microscopy and gene expression via RNA sequencing.

"This study is unique in that it is the first time we've applied spatial transcriptomics to fat tissue, which has a special set of characteristics
and composition," says Patrik Staahl, the study's third corresponding
author. "We are very happy that the technology continues to contribute
to solving biologically complex questions in an increasing number of
research areas." The research has been financed by donations from the Margareta af Uggla's foundation, Knut & Alice Wallenberg's foundation,
the Swedish Research Council, ERC-SyG SPHERES, the NovoNordisk Foundation,
the MSAM consortium, the MeRIAD consortium, CIMED, the Swedish Diabetes Foundation, Region Stockholm, the Erling-Persson Family Foundation and
the Strategic Research Program in Diabetes at Karolinska Institutet.

Patrik Staahl, Nayanika Bhalla and Alma Andersson are scientific
consultants to 10x Genomics which holds the IP rights to the spatial transcriptomics technology. Lovisa Franze'n is employed by Astra
Zeneca. No other declarations of interests have been reported.

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Jesper Ba"ckdahl, Lovisa Franze'n, Lucas Massier, Qian Li, Jutta
Jalkanen, Hui Gao, Alma Andersson, Nayanika Bhalla, Anders Thorell,
Mikael Ryde'n, Patrik L. Staahl, Niklas Mejhert. Spatial mapping
reveals human adipocyte subpopulations with distinct sensitivities
to insulin.

Cell Metabolism, 2021; DOI: 10.1016/j.cmet.2021.07.018 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210810110945.htm

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