Related Experiment Video
Updated: Jul 10, 2026
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice
Andréa L Rocha1, Christian Schmedt2,3, Guy Perkins4
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.
Abstract:
Uncovering the role of upstream open reading frames (uORFs) challenges conventional views of one protein per messenger RNA and reveals the capacity of some uORFs to encode microproteins that contribute to cellular biology and physiology. This study explores the functional role of a recently identified mitochondrial microprotein, SLC35A4-MP, in the brown adipose tissue of mice. Our findings reveal dynamic regulation of SLC35A4-MP expression during primary brown adipocyte differentiation in vitro and during cold exposure or high-fat diet (HFD)-induced obesity in mice. Using a knockout mouse model, we show that loss of SLC35A4-MP disrupts mitochondrial lipid composition, decreasing cardiolipins and phosphatidylethanolamine in brown adipose tissue from HFD-fed mice. SLC35A4-MP deficiency also impairs mitochondrial activity, alters mitochondrial number and morphology, and promotes inflammation. Knockout mice accumulate acylcarnitines during cold exposure, indicating defective fatty acid oxidation. These findings reveal SLC35A4-MP as a previously unrecognized microprotein in regulating mitochondrial function and tissue lipid metabolism, adding to the growing list of functional endogenous microproteins.
Insights
This study identifies a novel microprotein, SLC35A4-MP, crucial for brown adipose tissue function. Its absence impairs mitochondrial health and lipid metabolism, particularly under cold or high-fat diet conditions.
Area of Science:
- Mitochondrial biology
- Gene expression regulation
- Metabolic research
Background:
- Upstream open reading frames (uORFs) challenge the traditional view of gene expression, enabling the production of microproteins.
- Microproteins are increasingly recognized for their roles in cellular functions.
- The specific functions of many microproteins, especially in metabolic tissues, remain largely unexplored.
Purpose of the Study:
- To investigate the functional role of the microprotein SLC35A4-MP in mouse brown adipose tissue.
- To determine how SLC35A4-MP expression and function are affected by differentiation, cold exposure, and high-fat diet (HFD).
Main Methods:
- Analysis of SLC35A4-MP expression during brown adipocyte differentiation in vitro.
- Assessment of SLC35A4-MP regulation in mice exposed to cold or HFD.
- Generation and characterization of a SLC35A4-MP knockout mouse model.
- Mitochondrial lipid composition, activity, morphology, and inflammation assays.
- Acylcarnitine profiling in knockout mice under cold exposure.
Main Results:
- SLC35A4-MP expression is dynamically regulated during brown adipocyte differentiation and in response to cold or HFD.
- Loss of SLC35A4-MP in knockout mice alters mitochondrial lipid composition (decreased cardiolipin and phosphatidylethanolamine) in brown adipose tissue from HFD-fed mice.
- SLC35A4-MP deficiency impairs mitochondrial activity, alters mitochondrial number and morphology, and promotes inflammation.
- Knockout mice exhibit acylcarnitine accumulation during cold exposure, indicating defective fatty acid oxidation.
Conclusions:
- SLC35A4-MP is a novel microprotein that plays a significant role in regulating mitochondrial function and lipid metabolism in brown adipose tissue.
- This microprotein is essential for maintaining metabolic homeostasis under conditions of cold stress and high-fat diet.
- The findings expand the known repertoire of functional endogenous microproteins and their physiological importance.
More Related Videos
04:46Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
02:55Author Spotlight: Illuminating New Avenues for Adipose Tissue Metabolism and Disease Prevention
Published on: October 6, 2023
