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CNIC identifies key mechanism in fat cells to combat obesity

Posted: 2 December 2024 | | No comments yet

CNIC researchers have identified a mechanism in fat cells that helps them safely store excess fat, offering new insights for combating obesity and related metabolic diseases.

Fat cells, adipocytes and lipocytes

A team of researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), led by Professor Miguel Ángel del Pozo Barriuso, has uncovered an essential mechanism in fat cells (adipocytes) that enables them to safely store excess fat, avoiding damage to tissues and organs. This breakthrough, published in Nature Communications, opens the door to new therapeutic strategies for treating obesity, lipodystrophy, metabolic syndrome, and other diseases linked to fat accumulation.

The role of fat cells in metabolic health

In modern societies characterised by sedentary lifestyles and high-calorie diets, adipose tissue plays a vital role in metabolic health. Adipocytes store fat as an energy reserve, preventing the accumulation of excess lipids in critical organs, such as the liver and blood vessels. These excess lipids can lead to severe damage and conditions such as cardiovascular disease and fatty liver disease. However, this process is not without risks. When adipocytes become overloaded with fat, they can rupture, releasing toxic molecules and triggering inflammation, which disrupts metabolism.

The CNIC team set out to understand how adipocytes adapt to mechanical stress as they expand to store excess fat. Their research focused on caveolae, small invaginations in the cell membrane that act as sensors and shock absorbers for these stresses. According to the study’s first author, Dr María Aboy Pardal said, “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.”

This process protects the adipocytes from rupture and prevents the inflammatory responses associated with fat cell damage. However, caveolae do more than provide structural support, they also play a critical role in regulating metabolism. During adipocyte expansion, caveolae send signals to other parts of the cell, adjusting metabolic activity to match energy reserves. “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,” explained del Pozo Barriuso.

Implications for metabolic diseases

When caveolae are absent or malfunctioning, adipocytes become more rigid and vulnerable to damage. This impairs their ability to store fat and maintain cellular integrity. This dysfunction is linked to conditions such as lipodystrophy, where the body cannot store fat properly, resulting in severe metabolic disturbances.

The study further revealed the importance of the protein caveolin-1 (Cav-1), which is necessary for caveolae to flatten in response to mechanical stress. Cav-1 must undergo a chemical modification known as phosphorylation, where a phosphate group is added to a specific amino acid. Researchers created a transgenic mouse model that expressed a version of Cav-1 unable to be phosphorylated. In these mice, adipocytes could not expand correctly in response to fat accumulation, leading to conditions resembling lipodystrophy and underscoring the critical role of Cav-1 in maintaining adipocyte function.

A step toward therapeutic solutions

“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 minimising organismal damage,” said Del Pozo Barriuso

The study, which involved collaboration with CNIC’s Transgenesis, Pluripotent Cell Technology, Microscopy, and Histopathology units, as well as researchers from the Instituto de Ciencia de Materiales de Madrid (ICMM) and CIMUS, represents a major step forward in understanding how fat cells protect the body from the harmful effects of excessive fat storage.

This study was published in Nature Communications.

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