Central regulator discovered: researchers now striving to tune metabolism

Diet and lifestyle 1. mar 2018 2 min Assistant professor Yang de Marinis Written by Morten Busch

Obesity, diabetes, cardiovascular disease and other diseases resulting from imbalanced metabolism are hitting record highs worldwide. Our changing diet and sedentary lifestyles warn of the increasing challenges ahead. Researchers have recently discovered a protein that is present throughout the body and regulates our metabolism. The researchers hope to learn how to increase and decrease the quantity of this protein and thereby regulate metabolism.

The number of people with diabetes has exploded globally, but the incidence of diabetes in Norway declined dramatically for a brief period between 1939 and 1945 when Germany occupied Norway during the Second World War. The German troops confiscated the livestock, and Norwegians therefore mostly ate grains, vegetables and fruit. 

This example shows how dietary changes and restricting the quantity of energy consumed can lead to a decline in the number of people with metabolic diseases. Today, however, global metabolism is out of control, but researchers from Lund University in Sweden have found a key switch that may help to regulate metabolism.

“We have found a switch – a protein called NRIP1 [nuclear receptor–interacting protein 1] – that can either boost or slow down our metabolism. It may help us to regulate our metabolism in cases such as obesity. Our research also shows that exercise can activate this switch,” explains the lead author, Yang De Marinis, Assistant Professor, Lund University.

The body remembers weight loss

NRIP1 is present in almost all tissues in our body, but fatty tissue and skeletal muscle have the highest concentrations. In their study, the researchers measured NRIP1 levels in both tissue and blood in connection with weight loss and exercise conditions.

“In our weight-loss study, NRIP1 was especially interesting because, among all known metabolic genes, NRIP1 was the only gene that showed strong link to metabolic changes after weight-loss. NRIP1 functions as a reverse switch: when NRIP1 is high, metabolism is suppressed; when NRIP1 is low, metabolism speeds up.”

In contrast to what we might think, obese people usually have a higher resting metabolic rate and energy consumption compared with people of normal weight because they have more fatty tissue and muscle mass.

“We found that, when obese people lost weight, the levels of NRIP1 in fatty tissue and blood rose and their metabolism decreased. We also found that the body remembered the increase for up to 6 months after the weight-loss study ended.”

Learning to activate the switch

The researchers also studied how accelerated metabolism during exercise affects NRPI1 levels among healthy, non-obese people. As expected, NRIP1 gene expression levels in skeletal muscles were reduced after exercise because of a higher metabolic rate. However, there was also another unexpected and surprising discovery.

“NRIP1 concentrations increased in the participants in the control group, who were sedentary instead of taking exercise. We can compare this with our everyday sedentary lifestyles. For example, sitting in front of a computer for 2 hours is enough to double your NRIP1 levels and significantly slow down your metabolism.”

Human metabolism is thus far from simple, and this new discovery sheds light on how this new molecular switch could regulate metabolism up or down by, for example, changing lifestyle.

“We are currently working on further understanding the molecular mechanisms of NRIP1 as a metabolic switch. In this study, we have identified it as a very important protein in human metabolism. In the long term, we hope to learn how to boost or slow down metabolism by applying this switch,” concludes Yang De Marinis.

Regulation of nuclear receptor interacting protein 1 (NRIP1) gene expression in response to weight loss and exercise in humans” was published in Obesity in 2017. The Novo Nordisk Foundation awarded Martin Ridderstråle, the senior author of this study, a grant in 2013 for the project Clinical and Genetic Characteristics of Human Obesity and Weight Reduction.

Assistant Professor Yang De Marinis, PhD, is a principle investigator at Lund University Diabetes Centre, Sweden. Her research team is focusing on epi...

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