A diet with too many calorie restrictions can be bad for the kidneys – News

A diet with too many calorie restrictions can be bad for the kidneys – News

Experiments with mice were performed in USP (University of Sao Paulo) indicate that the kidneys react differently from other organs a calorie-restricted diet and, in the long run, can suffer damage.

The research line is coordinated by a professor at the Institute of Chemistry (IQ-USP) Alicia Kowaltowskiwithin the Research Center in Redox processes in biomedicine (Redoxoma)FAPESP Center for Research, Innovation and Dissemination (CEPID).

The latest results are published in American Journal of Physiology-Renal Physiology.

Kowaltowski’s group was dedicated to understanding how dietary changes affect metabolism and modulate the risk of aging-related diseases. One of the main focuses is research on the effect caloric restriction of mitochondria – organelles responsible for providing energy for the functioning of cells.

Previous work done on mice has found that a low-calorie diet improves pancreatic function and can protect the brain from the death of neurons associated with diseases such as Alzheimer’s disease, Parkinson’s, epilepsy i cerebrovascular infarction (stroke), among others. Benefits for the liver, skin, and even for stimulating hair growth have also been observed.

In the latest study, researchers compared the mitochondria of the kidneys of rats fed a 40% calorie diet (no malnutrition) for six months with those in the control group, in which the animals ate freely and remained sedentary, becoming obese.

“That 40% reduction sounds like a lot to a normal human being, but it’s a reduction compared to animals kept in a laboratory, eating unrestricted and really obese,” says Kowaltowski.

The experiment showed that the mitochondria of the kidneys of mice that are subject to calorie restriction produce more free radicals – unstable molecules that damage cell structures in excessive amounts. This makes the organelles incapable of properly controlling the entry of calcium into their interior, compromising the synthesis of ATP (adenosine triphosphate, the “fuel” of the cell) and leading to cell death.

The study also showed, for the first time, that caloric restriction regulates calcium uptake into mitochondria by modulating MICU2 protein.

“Interestingly, we have shown a mechanism by which the production of more oxidants causes mitochondria to be less able to retain calcium and become more susceptible to oxidative damage. By correcting this defect with antioxidants, the mitochondria of animals that are subject to calorie restriction are returned to those of control animals, ”says chemist Julian David Cualcialpud Serna, the first author of the article and a doctoral student at FAPESP.

unexpected result

The kidneys need a lot of energy to filter the blood, and due to their high metabolic activity, they have a lot of mitochondria. However, according to Kowaltowski, there is little research on the effects of calorie restriction on this organ.

“Our group considered calorie restriction and what it does to mitochondria in terms of free radical production and in terms of their key functions, such as oxidative phosphorylation, which creates ATP, and calcium transport. A few years ago, we saw that calorie restriction altered calcium transport in the brain and liver. Now we decided to look at the kidney and we were surprised by the results “, says the teacher.

What surprised scientists was that, contrary to what happens in other tissues, the mitochondria of the kidneys of lean animals produce more free radicals. In them, faster calcium intake was accompanied by increased production of hydrogen peroxide, a strong oxidant. According to the authors, the higher release of hydrogen peroxide increases the tendency to pass calcium-induced permeability, because the process is associated with the oxidation of thiol membrane proteins. The effect is reversed by the use of the antioxidant dithiothreitol.

Known mainly for being part of our bone structure, calcium performs several functions and is essential for the functioning of our body because it is found in soluble form in body fluids, inside and outside cells. It is an important signal in processes such as muscle contraction, cell differentiation and inflammation, among others. Furthermore, it is a central regulator of cellular functions, controlling metabolism in several aspects, for example, by regulating ATP production, glycogen breakdown, and glycolytic pathway. Mitochondria capture and store calcium, maintaining its intracellular concentration at the physiological level.

“Mitochondria can react to what is happening around them in several ways, and one of them is through a calcium signal. Taken in small amounts and for shorter periods of time, calcium activates mitochondria. But, excessively, it leads to mitochondrial damage. And if the mitochondria are damaged, they stop working, they stop producing energy for the cell, ”explains Serna.

In mitochondria, calcium uptake into the mitochondrial matrix occurs through the mitochondrial uniporter channel (MCU) and is driven by the potential of the inner mitochondrial membrane, which attracts positively charged species. MCU is a complex formed of several proteins. One of them is MICU2, which acts as a negative regulator. That is, in the absence of this protein, calcium enters the mitochondria faster.

“What we have noticed is that in animals under calorie restriction this protein is reduced and there is a higher calcium intake. This is new, it has never been seen that diet changes this protein in a physiological context, ”says the researcher.

Thus, the renal mitochondria of calorie-restricted animals absorb calcium faster than those of control animals, but are the first to be injured because their ability to store these ions is reduced. This means that animals under calorie restriction live longer, are healthier in many ways, but in a situation where they are prone to kidney damage for other reasons, a slightly higher weight may be more favorable.

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