Retinoic acid (RA) is a derivative of vitamin A. A study originating from the University of Montreal and CHUM research (CRCHUM) demonstrated the impact of RA on obesity, type 2 diabetes and cardiovascular disease, The research findings were presented on June 6th 2014 at the Annual Conference of the Canadian Nutrition Society in Saint John’s Newfoundland and focused on the fact that RA reduces cell death (apoptosis).
“In obese and insulin resistant mice, retinoic acid reduces the risk of cardiac apoptosis, stimulates the expression of cardio-protective genes reduced by the disease, and protects against the accumulation of collagen in the cardiac muscle, thus avoiding the occurrence of fibrosis and possible associated future complications,” said the first author of the study, Daniel-Constantin Manolescu.
“Blood glucose, insulin resistance, body weight, and adipocyte size were significantly decreased in treated animals, including abdominal fat, while dietary intake and physical activity were similar for treated or non-treated animals. This suggests an increase in basal energy expenditure,” said Manolescu.
The researchers hypothesize that RA is directly involved in differentiating between brown and white fat. Fat acts an energy reserve but white and brown fat has a different metabolic function. White fat not only acts as an energy reserve, storing triglycerides, but is involved in controlling the hormonal balance in the body. If energy intake through food consumption is greater than energy expended, obesity increases, while hormonal balance and energy metabolism are disturbed. Resistance to type 2 diabetes develops over time.
Brown fat also stores triglycerides, but it has the ability to produce heat, required for an active metabolism. Brown fat is irrigated by blood vessels and has many mitochondria, the energy factories of cells. Retinoic acid acts by stimulating a mitochondrial uncoupling protein (UCP1) that allows uncoupling of the mitochondria pathway (oxidative phosphorylation ), which uses energy from the oxidation of nutrients for the production of adenosine triphosphate (ATP). In this way heat is generated (thermogenesis) instead of ATP, which is traditionally the energy required for active metabolism. Exposure to cold leads to the stimulation of brown fat and white fat, promoting the conversion of triglycerides to free fatty acids and glycerol. In brown adipocytes, these fatty acids are rapidly oxidized in the mitochondria and produce heat (under the influence of the UCP1 protein). Brown fat therefore helps to increase basal energy metabolism. As a result, hibernating mammals fatten in the fall without developing diabetes and lose weight without moving too much in the winter (while warming their den). They are also the animals that accumulate the most Vitamin A in their livers. Retinoic acid (a Vitamin A derivative) is recognized for its involvement in cell maturation and differentiation and may guide pre-adipocytes to become brown (or beige) instead of white.
“Our studies on animals show that retinoic acid induces normalization of blood glucose and reduction of obesity. It is an important contribution to understanding RA action on the liver, fat, muscles, and the heart, and on retinoid metabolism, energy metabolism, fatty acid oxidation, and insulin resistance. Our research identifies new metabolic effects of retinoids and may lead to anti-obesity and anti-diabetic medicines,” said Dr. Jean-Louis Chiasson, another researcher involved in presenting the findings of this study.
Daniel-Constantin Manolescu, Marek Jankowski, Bogdan Alexandru Danalache, Donghao Wang, Tom L Broderick, Jean-Louis Chiasson, Jolanta Gutkowska. All-trans retinoic acid stimulates gene expression of the cardio-protective natriuretic peptide system, and prevents fibrosis and apoptosis in cardiomyocytes of obese ob/ob mice. Applied Physiology, Nutrition, and Metabolism, 2014; 140430143753005 DOI: 10.1139/apnm-2014-0005