- Intense negative tone.
A high-fat diet can lead to metabolic dysfunction, including weight gain and increased risk of diabetes. Researchers have identified key enzymes affected by a high-fat diet, offering new avenues for research into obesity-associated metabolic disorders.
Consuming a high-fat diet can lead to a variety of health problems — not only weight gain but also an increased risk of diabetes and other chronic diseases. At the cellular level, hundreds of changes take place in response to a high-fat diet.
A high fat diet is characterized by a significant increase in dietary fat intake, often exceeding the recommended daily allowance.
This type of diet can be further divided into two categories: low-carb high-fat (LCHF) and ketogenic diets.
LCHF diets aim to reduce carbohydrate consumption while increasing fat intake, whereas ketogenic diets focus on achieving a specific metabolic state by drastically reducing carb consumption and increasing fat intake.
Research suggests that high fat diets may aid in weight loss and improve certain health markers, but their long-term effects are still being studied.
The Effects on Metabolic Enzymes
MIT researchers have now mapped out some of those changes, with a focus on metabolic enzyme dysregulation that is associated with weight gain. Their study, conducted in mice, revealed that hundreds of enzymes involved in sugar, lipid, and protein metabolism are affected by a high-fat diet.
Phosphorylation and Metabolic Networks
The researchers found that many of the metabolic enzymes that undergo phosphorylation belong to a class called oxidoreductases, which transfer electrons from one molecule to another. Such enzymes are key to metabolic reactions such as glycolysis — the breakdown of glucose into a smaller molecule known as pyruvate.
Phosphorylation is a fundamental biochemical process where a phosphate group is added to a protein, altering its function.
This modification can activate or deactivate enzymes, receptors, and other proteins, influencing various cellular activities such as metabolism, signaling, and gene expression.
Phosphorylation occurs through the action of kinases, which transfer phosphate groups from high-energy molecules like ATP.
It plays a crucial role in many biological processes, including cell growth, differentiation, and apoptosis.
Redox Imbalance and Insulin Resistance
Phosphorylation of these enzymes can lead them to become either more or less active, as they work together to respond to the intake of food. Most of the metabolic enzymes identified in this study are phosphorylated on sites found in regions of the enzyme that are important for binding to the molecules that they act upon or for forming dimers — pairs of proteins that join together to form a functional enzyme.
Sex-Specific Metabolic Reprogramming
The effects were more pronounced in male mice than female mice. Female mice were better able to compensate for the high fat diet by activating pathways involved in processing fat and metabolizing it for other uses.
Metabolic reprogramming refers to the regulation of cellular metabolism in response to changing environmental conditions.
Research has shown that sex-specific metabolic reprogramming occurs due to differences in sex hormones, such as estrogen and testosterone, which influence gene expression and enzyme activity.
This phenomenon contributes to gender differences in metabolic disorders, including obesity and diabetes.
Studies have demonstrated that males exhibit increased glucose tolerance and insulin sensitivity compared to females, who are more prone to developing type 2 diabetes.
Reversing the Effects of a High-Fat Diet
However, if they gave mice who were on a high-fat diet an antioxidant called BHA, many of these effects were reversed. These mice showed a significant decrease in weight gain and did not become prediabetic, unlike the other mice fed a high-fat diet.
A New Perspective on Metabolic Health
The researchers’ study suggests that there is something biochemically happening in cells to bring them to a different state — not a normal state, just a different state in which now, at the tissue and organism levels, the mice are healthier. This finding opens up new avenues for research into the prevention or treatment of obesity-associated metabolic dysfunction.
Future Directions
In her new lab at the University of North Carolina, Tamir now plans to further explore whether antioxidant treatment could be an effective way to prevent or treat obesity-associated metabolic dysfunction, and what the optimal timing of such a treatment would be.
