P. Macedo Lab | Fats or Sugars: What are the main enemies of metabolic diseases?

What is the impact of high fat diets and high fructose diets on metabolic diseases such as obesity, type 2 diabetes and Non-Alcoholic Fatty Liver?


Maria João, Paula Macedo e Inês Lima

This question is answered in the research led by Paula Macedo, from the MEDIR group. In the article published in the journal Frontiers in Endochronology, the researchers suggest that specific excesses in human diet may differentially influence the premature onset of metabolic disorders. This is what we discussed with the first author of the study, Maria João Meneses:

What discoveries led you to the research described in your publication?

Although awareness for metabolic disorders such as obesity and type 2 diabetes mellitus has increased over the years, its prevalence in the population continues to increase dramatically. Most of the cases are due to excessive consumption of highly processed and energy dense foods, frequently combined with a sedentary lifestyle.

These lifestyle habits lead to metabolic and homeostatic dysfunctions that may end up in the onset of hypertension, type 2 diabetes mellitus, cardiovascular disease, alterations in blood lipids (dyslipidemia) and non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease in Western countries, having a reported prevalence of 6-35% worldwide. The overload of lipids/fat and sugars from the diet affects not only the liver, but other metabolic organs such as the muscle or adipose tissue. Considering organ specificities, dysfunctions in one of these organs will impact on others, namely in cases of insulin resistance and inflammation, and alterations in metabolism overall.

What were you trying to understand and what is the main discovery of this work?

We hypothesized that dietary content in lipids or sugars differentially affect the metabolic network (metabolome) of insulin-sensitive organs. Regarding sugars, we focused on fructose, that is present in soft drinks and in high-fructose corn syrup, a sweetener commonly used to enhance the flavor of foods and beverages. Our aim in this study was to evaluate the metabolome of insulin sensitive organs, as is the case of the liver, muscle and white and brown adipose tissue in animals fed with high-fat or high-fructose diet. Indeed, our data illustrate that high-fat and high-fructose diets have a negative but distinct impact on the metabolome of liver, muscle, and adipose tissue.

Why is this important? 

As mentioned, and given the link between the increased consumption of fat and sugars and the increased prevalence of metabolic disorders, it is crucial to unveil diet effects’ on insulin sensitive tissues, such as the liver, the muscle and the adipose tissue and how it can contribute for the onset of metabolic disorders.

Can you use an analogy to help us understand your work?

Metabolites in tissues can vary substantially over a variety of environmental conditions and biological factors, such as the diet and/or diseases. Moreover, these metabolites vary differently between tissues. Here, we wanted to understand how saturated fats and fructose affect metabolic disorders, so we used different diets, either rich in lipids or rich in fructose to mimic human diets containing highly processed foods. These tested diets in animal models, rich in lipids or fructose, are comparable to humans consuming fast foods or soft drinks, respectively. This characterization of metabolites resulting from different diets, with the high fat diet being the most dangerous, can be the stepping stone for future studies on the role of these specific metabolites for the development of metabolic disorders

What questions remain to be asked?

Each and every one of us has a unique diet. Herein, we address a very specific lipid and fructose-enriched diets. However, there are other sugars that have negative effects as well as different mixtures of lipids and most of them remain to be addressed. Moreover, in this work we evaluated specific insulin sensitive tissues. In the future we need to evaluate other organs and plasma.

Read full article here:

Meneses MJ, Sousa-Lima I, Jarak I, Raposo JF, Alves MG, Macedo MP. Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view. Front Endocrinol (Lausanne). 2022 Aug 17;13:898471. doi: 10.3389/fendo.2022.898471