Adipocytes differentiated in vitro, containing fats deposits (yellow) and the Cav-1 protein within the cell membrane (magenta). Scale bar, 100 microns. b, Mouse adipose tissue. Scale bar, 100 microns. c, Electron microscopy pictures exhibiting areas of adipocyte membrane much like that indicated by the boxed space in b. Caveolae are seen as membrane invaginations (arrowheads). The genetically modified adipocyte expressing non-phosphorylatable Cav-1 (backside panel) accumulates caveolae as a result of they can not flatten in response to the buildup of fats (blue arrowheads). Scale bar, 500 nm. Credit score: CNIC
A analysis workforce has recognized a vital mechanism in fats cells (adipocytes) that allows them to enlarge safely to retailer power. This course of avoids tissue injury and protects the physique from the poisonous results of accumulating fats molecules (lipids) in inappropriate locations.
The outcomes, printed in Nature Communications, signify a significant advance within the understanding of metabolic ailments. Furthermore, this discovery opens the door to the event of latest therapeutic methods to fight ailments associated to power energetic extra, equivalent to chubby, weight problems, lipodystrophy, and metabolic syndrome, and their grave cardiovascular and metabolic issues.
In trendy societies, characterised by sedentary existence and high-calorie diets, adipose tissue is a key determinant of metabolic well being. Adipocytes can enlarge to retailer power within the type of fats, stopping extra lipids from accumulating in organs just like the liver or within the blood vessel wall (particularly within the coronary heart and the mind), the place they might trigger irreparable injury.
However, this course of is just not risk-free. When adipocytes are overloaded with fats they will rupture, releasing their poisonous contents and producing irritation and metabolic alterations.
The Centro Nacional de Investigaciones Cardiovasculares (CNIC) research examined how adipocytes adapt to face up to the mechanical stress related to their enlargement to accommodate an extra of fats.
The workforce—led by Professor Miguel Ángel del Pozo Barriuso, who heads the Mechanoadaptation and Caveolae Biology group on the CNIC—analyzed the function of caveolae, small invaginations within the cell membrane that act as sensors and shock absorbers of those stresses.
“When an adipocyte accumulates fat and its surface is under increased tensile stress, the caveolae flatten, releasing a ‘reservoir’ of membrane that allows the cell to enlarge without breaking apart. Conversely, when fat reserves diminish, these structures regroup to reduce the excess membrane and restore cellular stability,” defined research first writer Dr. María Aboy Pardal.
Caveolae: Not only a structural help
In addition to bodily defending adipocytes, caveolae additionally play a vital function in coordinating cell metabolism. Prof. del Pozo Barriuso defined that in adipocyte enlargement, “molecular components of these membrane structures travel to other cell compartments, conveying signals that adjust metabolic activity to match the level of energy reserves. This capacity for internal communication makes caveolae key elements for efficient caveolar function.”
Nevertheless, when these constructions are absent or malfunction, adipocytes grow to be extra inflexible, susceptible to rupture, and fewer environment friendly at storing power. The end result, added Dr. Aboy Pardal, “is an inflammatory reaction that compromises the body’s metabolic health. This phenomenon is linked to conditions such as lipodystrophy, in which the body cannot store fat, leading to severe metabolic and cardiovascular alterations.”
The CNIC research highlights the important thing function of the caveolae protein caveolin-1 (Cav-1). For caveolae to flatten accurately in response to fluctuations in mechanical pressure within the cell membrane, Cav-1 have to be chemically altered by the addition of a phosphoryl group to a particular amino acid, a course of known as phosphorylation.
For the research, the researchers developed a transgenic mouse that expresses a genetically altered model of Cav-1 that can not be phosphorylated. This renders adipocytes unable to increase accurately in response to the mechanical pressure generated by the buildup of lipids, severely limiting their capability to retailer power and keep mobile integrity. The failure of this easy mechanism in the end results in lipodystrophy and its extreme penalties.
Dr. del Pozo Barriuso concluded, “These results give us a better understanding of how adipose tissue responds to the mechanical forces associated with energetic excess. In the context of obesity and metabolic syndrome, this protective mechanism is essential for minimizing organismal damage.”
Extra data:
Plasma membrane transforming determines adipocyte enlargement and mechanical adaptability, Nature Communications (2024). DOI: 10.1038/s41467-024-54224-y
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Centro Nacional de Investigaciones Cardiovasculares
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Group discovers {that a} key mechanism in fats cells protects the physique in opposition to energetic extra (2024, November 28)
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