New insights into metabolic adaptation to nutritional changes

June 06, 2024

How does our body adapt to fluctuations in nutrient availability? What are the molecular mechanisms that enable our cells to cope with these changes, and what happens when these systems fail during chronic overnutrition, leading to obesity?

A recent UC Berkeley-led study published in Nature Communications details how liver cells reorganize their internal membrane structures to adapt to changes in nutrient availability. Using advanced nanometer-resolution volumetric 3D electron microscopy combined with artificial intelligence-based automated image annotation, researchers in the lab of Nutritional Sciences and Toxicology (NST) professor Ana Paula Arruda found that cycles of fasting and feeding cause dynamic remodeling of the organelles endoplasmic reticulum (ER) and mitochondria in the liver.

According to first author Güneş Parlakgül, an assistant adjunct professor in NST, the researchers observed that mitochondria in the fasted state become elongated, and the rough ER forms extensive areas of interaction with the mitochondria. This remodeling, in turn, regulates the function of these organelles, allowing them to adapt and respond to limited nutritional availability during fasting. 

Importantly, Parlakgül notes, the study shows that the dynamic regulation of organelle structure in response to fasting and feeding is defective in obese animals, and rescuing this regulation improves the metabolic function of the cells. “Structural plasticity and the reorganization of the subcellular environment are critical for adapting to changes in metabolic demand,” he said.

These findings offer a new perspective to understand metabolic regulation and may lead to the identification of potential targets for treating metabolic diseases such as obesity, diabetes, and fatty liver disease in the future.

Read the full article in Nature Communications

The study was conducted in collaboration with researchers from Harvard University and Yale University. More videos related to this study can be viewed on YouTube.