They discovered a key mechanism in fat cells

This process prevents tissue damage and protects the body from the toxic effects of fat accumulation in inappropriate places. Results published in the journal Natural communications, They represent significant advances in the understanding of metabolic diseases.

Moreover, this discovery opens the door for development of new therapeutic strategies to combat comorbidities with chronic excess energy such as overweight, obesity, lipodystrophy and metabolic syndrome, as well as their serious cardiovascular and metabolic complications.

In a society characterized by a sedentary lifestyle and a high-calorie diet, adipose tissue plays a critical role in metabolism. Adipocytes have the ability to greatly expand to store energy as fat, preventing excess lipids from accumulating in organs such as the liver or blood vessel walls (especially the heart and brain), where they can cause irreversible damage.

However, this process is not without risks: excess fat can cause adipocytes to break down, releasing their toxic contents and causing inflammation and metabolic changes.

CNIC research focuses on how adipocytes adapt to withstand mechanical stresses resulting from their expansion to accommodate stored fat.

The team analyzed the role of caveolae, small depressions in the cell membrane that act as sensors and buffers of these stresses. “When an adipocyte accumulates fat and its surface is subjected to greater stress, the caveolae flatten, releasing a membrane “reservoir” that allows the cell to expand without collapsing. On the other hand, when fat stores are reduced, these structures rearrange to reduce excess membranes and restore cellular stability,” explains the researcher. Dr. Maria Aboy Pardalfirst author of the study.

Caveolae: More than Structural Support

In addition to physically protecting adipocytes, caveolae play an important role in coordinating cellular metabolism. During the expansion process, describe in detail Dr. Miguel Angel del Pozo Barriuso“The molecular components of these structures move to other compartments of the cell, sending signals that regulate metabolic activity in accordance with the level of energy reserves. This ability to ‘communicate’ internally makes caveolae key elements for efficient adipocyte function.”

However, when these structures are missing or do not function properly, adipocytes become stiffer, more vulnerable to rupture, and less efficient at storing energy. The result, adds Dr. Aboy Pardal, “is inflammation and the metabolic health of the body is compromised. This phenomenon is associated with diseases such as lipodystrophy, a condition in which patients are unable to form fat deposits, leading to severe metabolic and cardiovascular changes.

Likewise, the CNIC study highlights the role of the key protein caveolin-1 (Cav1) in the process of caveolae reorganization. This protein needs to be phosphorylated (chemically modified) at a specific amino acid so that caveolae can flatten properly in response to fluctuations in mechanical stress in the cell membrane.

The researchers developed a transgenic mouse that expressed a modified form of Cav1 that was resistant to phosphorylation. In this mouse, that is, when Cav1 phosphorylation does not occur, adipocytes cannot expand properly under the stress created by fat accumulation (see image), which negatively affects their ability to store energy and maintain cell integrity. Disruption of this basic mechanism ultimately leads to lipodystrophy and its serious consequences.

Obesity

Professor Miguel Angel del Pozo concludes that “these results allow us to better understand how adipose tissue responds to the mechanical forces associated with excess energy. In the context of obesity and metabolic syndrome, this protective mechanism is key to minimizing damage to the body.”

The research was conducted in collaboration with the departments of transgenesis, pluripotent cell technology, microscopy and histopathology of the CNIC. Additionally, researchers from the Madrid Institute of Materials Science (ICMM, CSIC) collaborated; CIMUS Research Center for Molecular Medicine and Chronic Diseases; CNIO; Biomedical Research Institute “Sols-Morreale”; and the Margarita Salas Center for Biological Research – CSIC.

Help Article:

Aboy-Pardal MKM, Guadamillas MK, Guerrero CR, Catala-Montoro M, Toledano-Donado M, Terres-Dominguez S, Pavon DM, Jimenez-Jiménez V, Jimenez-Carretero D, Zamai M, Folgueira S, Cerezo A, Lolo FN , Nogueiras R., Sabio G., Sanchez-Alvarez M., Echarri A., Garcia R., Del Nu MA. Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability.. National Commun. Accepted November 5, 2024. In press. doi:10.1038/s41467-024-54224-y

Fountain: Central Scientific Research Center