Culprit behind obesity-associated conditions identified

Washington, Feb 1 (ANI): Researchers have identified a target that could hold the key to developing safe therapies to treat obesity and its associated conditions such as type 2 diabetes, cardiovascular disease and stroke.

Although recent research has begun to unravel some of the pathways that control how information is processed by our nervous system regulating body weight and cardiovascular function, the exact mechanisms through which signals are sensed by the brain and translated into co-ordinated metabolic and cardiovascular responses remain unclear.

A University of Bristol team, with funding from the British Heart Foundation (BHF), has now identified that a target found to be critical in the brain's regulation of body weight, is also crucially involved in the development of obesity-associated conditions.

Researchers describe the mechanism behind a key molecule, known as melanocortin-4-receptor (MC4R), whose mutation or loss in both human and animal models has shown to cause severe obesity with type 2 diabetes.

While previous studies have shown that small activators of the molecule, which increase MC4R activity, have the desirable effect of reducing food intake and insulin secretion from the pancreas (important to suppress the development of type 2 diabetes), it is not clear how, at the same time, they trigger the undesirable effect of increasing blood pressure.

The team has now identified a mechanism for MC4R-mediated regulation of the activity of the autonomic nervous system to maintain appropriate blood pressure and insulin levels. The autonomic nervous system, which regulates internal organs and processes that are not under our control, is split into the parasympathetic and sympathetic nervous system, commonly exerting opposing influences on the structures they supply with nerves.

Researchers demonstrated that the activation of the MC4R inhibits parasympathetic neurons in the brain stem area of the central nervous system (CNS), while activating sympathetic neurons in the spinal cord. The team further demonstrates, in genetically-modified mouse models of human loss of MC4R function, that MC4Rs in these CNS areas are to blame for the development of obesity-induced increases in blood pressure.

They also reported that MC4Rs in these CNS areas are pivotal in maintaining appropriate insulin levels to stave off type 2 diabetes. Thus, by carefully balancing positive and negative forces on the autonomic nervous system, the MC4R maintains equilibrium of appropriate blood pressure and insulin levels. This is independent of the MC4R's role in the regulation of food intake elsewhere in the CNS.

MC4R is a target of intense pharmaceutical interest and the data from this research helps in our understanding of the CNS mechanisms regulating homeostatic body weight, blood pressure and insulin levels through a distributed network of MC4Rs. These findings may facilitate the development of appropriate, safe therapies to treat obesity and its associated conditions.

Dr Shannon Amoils, Research Advisor at the BHF, which part-funded the study, stated: "This research increases our understanding of how the nervous system affects our metabolism, and the development of high blood pressure due to obesity. With further knowledge of this complex area we hope scientists will be able to find safe and effective ways of treating obesity-related heart and circulatory disorders."

The findings were published in Cell. (ANI)

Matches

MORE TOP STORIES TODAY

On Now: Chennai vs Punjab

On Now: Chennai vs Punjab

MS Dhoni won the toss and opted to bat at Abu Dhabi. More »

Evenly matched Rajasthan and Hyderabad face-off

Evenly matched Rajasthan and Hyderabad face-off

A quality that defines Rajasthan and Hyderabad is consistency. Rajasthan was one among two teams to enjoy complete dominance at home last season. Hyderabad… More »

Beleaguered Yuvraj tees off to Sharjah's delight

Beleaguered Yuvraj tees off to Sharjah's delight

Yuvraj Singh was hardly convincing to begin with against Delhi, but a big dose of crowd support and a helping of poor bowling meant he had the opportunity… More »

Trott to take 'immediate break' from cricket

Trott to take 'immediate break' from cricket

The England and Wales Cricket Board (ECB) on Friday confirmed that batsman Jonathan Trott is to take another break from all cricket with immediate eff… More »

Fiery star Stokes bids to curb his temper

Fiery star Stokes bids to curb his temper

England all-rounder Ben Stokes admits he must keep his anger under control if he is to end his international exile. More »

Bangalore's arsenal blazes to victory

Bangalore's arsenal blazes to victory

Yuvraj Singh was back to his best in his first match for Royal Challengers Bangalore. More »

Pakistan cricketers face probe

Pakistan cricketers face probe

Pakistani cricket authorities have launched an investigation after a number of current international stars played in exhibition matches in the United States… More »

BCCI to meet before next court hearing

BCCI to meet before next court hearing

The BCCI will hold an emergent working committee meeting on April 20 to discuss the future course of action with regard to the Supreme Court hearing concerning… More »

Gavaskar wants a clean IPL

Gavaskar wants a clean IPL

"Integrity is non-negotiable..." says the BCCI's interim chief ahead of Season 7 of the tainted league. More »

Kallis, Narine star in KKR win

Kallis, Narine star in KKR win

An all-round display saw Knight Riders thump Mumbai Indians by 41 runs in the IPL-7 opener. More »

'Yak' Kallis still on top of his game

'Yak' Kallis still on top of his game

The 38-year-old South African veteran turned it on for Kolkata Knight RIders in the opening match of IPL-7. More »

Time for Chennai to enter familiar cocoon

Time for Chennai to enter familiar cocoon

Chennai have an emphatic 8-3 lead in the head-to-head with Punjab, with one game tied More »

Srinivasan named in fixing report: SC

Srinivasan named in fixing report: SC

The court emphasised that the tainted administrator can no longer work for the BCCI. More »

Yuvraj happy to play for RCB: Kohli

Yuvraj happy to play for RCB: Kohli

New-look RCB will play their first game of IPL-7 on Thursday. More »

IPL: News Line

IPL: News Line

A round-up of all the news from this season of the IPL. More »

Shane Watson issues moral warning

Shane Watson issues moral warning

'Everyone knows what is right and what is wrong and if you do the wrong thing it will be found out' More »

Why I'm not looking forward to the IPL

Why I'm not looking forward to the IPL

Welcome to another season of a league that many watch but few trust. More »

Johnson may quit T20s for Tests

Johnson may quit T20s for Tests

Australia's Mitchell Johnson may quit limited-overs cricket to prolong his test career with an eye on the 2015 Ashes series in England, the fast bowler… More »

Nepal players call off boycott

Nepal players call off boycott

Thaw in relations after formation of an advisory committee that would work in tandem with the Cricket Association of Nepal. More »

There's a lot going on: Fleming

There's a lot going on: Fleming

He experienced anxious moments in the lead-up to the tournament as the courts decided on whether to suspend the franchise, he said, but stressed that the… More »

Latif couldn’t work with tainted players

Latif couldn’t work with tainted players

Former Pakistan cricket captain Rashid Latif said Tuesday he turned down the job of national chief selector because he could not work with ex-players tainted… More »

We are not over-confident: Bailey

We are not over-confident: Bailey

Indian Premier League — George Bailey-led Kings XI Punjab will face Chennai Super Kings on Friday. More »

Taxing issue — BCCI hits roadblock

Taxing issue — BCCI hits roadblock

MoU between BCCI & its units to avoid double taxation delayed after a few decline to share details. More »

Big runs expected, with bat and ball

Big runs expected, with bat and ball

Royal Challengers Bangalore: Their main concern, once again, is the fast bowling More »