A study reveals that some people carry rare genetic changes associated with less fat in the liver and better blood sugar regulation. This finding is based on the sequencing of more than one million people. It points in particular to a gene called FNIP1, which helps control how energy is used and stored in cells.
The authors analyzed the parts of the DNA that serve to make proteins in 1,032,116 people from America, Europe, and Asia. They looked for rare variants associated with a blood marker linked to metabolism: the ratio between triglycerides and HDL cholesterol. In total, 59 independent genes were associated with this marker.
Illustration of DNA, the carrier of genetic information.
Pixabay
FNIP1 particularly caught their attention.
Approximately 0.01% of the people studied carried very rare variants capable of interrupting the normal production of the FNIP1 protein. In these carriers, the researchers observed a lower triglyceride-to-HDL ratio, less fat in the liver, and lower blood sugar levels. The distribution of body fat was also more favorable according to the measurements used in the study.
These associations indicate that within this large population, carriers of these variants more often displayed certain favorable parameters. The authors also reported an approximately 60% lower risk of cardiometabolic diseases among them. This group of diseases includes conditions related to the heart and metabolism.
To understand this link, the team then worked with human liver cells. Reducing FNIP1 activity increased fat breakdown and the activity of genes linked to lysosomes. These small cellular compartments participate in the recycling of many molecules. FNIP1 therefore appears to act as a brake on several mechanisms that consume or recycle energy.
The researchers also tested this idea in mice fed a high-fat diet. Simultaneously reducing the activity of Fnip1 and a related gene, Fnip2, in the liver limited weight gain and the accumulation of liver fat. The animals also responded better to insulin, the hormone that helps cells use blood glucose.
Modifying a gene in a person is not the immediate goal, and FNIP1 has other biological functions. The results identify this protein as a possible target for future drugs. It will be necessary to determine whether inhibiting it can reproduce the observed metabolic effects without causing undesirable effects.