A weighty issue: biggest losers have greater nerve activity

If you put a group of people on a calorie-restricted diet, you’ll see that some seem to lose weight easily, while others struggle to shed each pound. This difference doesn’t just come down to how much they eat or exercise – we’re beginning to realise that a person’s nervous system activity may also affect their weight-loss success.

These are the findings of a study I led at the Baker IDI Heart and Diabetes Institute, which is published in this month’s Journal of Clinical Endocrinology & Metabolism.

Excess weight

Around 60% of adult Australians are either overweight or obese, placing them at increased risk of chronic diseases such as type 2 diabetes, heart disease and cancer. Carrying excess weight also affects life-expectancy, quality of life and healthcare costs, making it one of the greatest public health challenges of our time.

Obesity is caused by a combination of lifestyle, environmental and biological factors. Changes in the global food system – which is producing more processed, calorie-dense foods – along with increasingly time-poor and sedentary lifestyles have led to an imbalance between food consumption and energy expenditure.

Beyond these modifiable factors are others that we can’t control —namely, our biology, which is estimated to contribute at least 40% to our body weight and shape. Biology includes our genetics, hormones, metabolism and nervous system activity. These each play an important role, not only in the development of obesity, but also in attempts to lose weight.

How are nerves involved?

The sympathetic nervous system subconsciously regulates many of the body’s physiological functions, including the resting metabolic rate (how much energy we burn during sleep and rest), the dissipation of calories after eating and drinking (known as the thermic effect of food) and the breakdown of fat during weight loss.

Our study examined the relationship between sympathetic nervous system activity and weight loss outcomes in a group of 42 obese individuals on a 12-week low calorie diet.

We measured the participants’ nerve activity using a technique called microneurography, where metal microelectrodes, similar to an acupuncture needle, are inserted into nerve fascicles (bundles of nerve fibers) in the lower leg. By manually counting the electrical activity – expressed as the number of bursts per minute – we could measure the nervous impulses travelling from the brain to the skeletal muscle.

We found that successful weight losers (who lost an average of 9 kilograms) had a higher resting nerve activity at the start of the program than the participants we categorised as weight-loss resistant (those who lost an average of 3 kilograms).

Successful weight losers also showed large increases in nerve activity after eating a high-carbohydrate meal, whereas the responses were completely blunted in weight-loss resistant subjects, suggesting they were less able to process the calories they consumed.

These findings present two opportunities:

(1) to identify those who would benefit most from lifestyle weight-loss interventions, and

(2) to develop weight-loss treatments that stimulate specific nervous activity.

While microneurography is a highly specialised technique limited to the realms of research laboratories, other more accessible measures of nerve activity may be used at a population level. The main chemical released from sympathetic nerves is noradrenaline. If we measured blood levels of this hormone in the fasting state and in response to food intake, it could be used as an index of sympathetic activity.

Over past decades, pharmaceutical companies have focused their development of anti-obesity drugs on products that enhance weight loss –and the sympathetic nervous system has been a logical target.

The ideal drug would be one that selectively stimulates metabolic efficiency (resting metabolic rate, dissipation of calories after eating or drinking and the breakdown of fat tissue) without unwanted side effects.

But because of the widespread distribution of the sympathetic nervous system within the body, any drug that stimulates this nerve activity can affect multiple organs and tissue sites. Unwanted side-effects of such drugs include increased heart rate and blood pressure, insomnia, dry mouth and constipation, which limit their long-term use.

Several phase three trials are currently testing the long-term safety and efficacy of drug combinations, which include a component that mimics the action of noradrenaline.

What if you are weight-loss resistant?

The good news is that moderate-intensity exercise can improve your body’s ability to burn calories after eating. Regular brisk walking, swimming or bike-riding may help improve your metabolic efficiency and allow you to lose more weight.

It’s also important to note that even modest weight loss will reduce your risk factors that are associated with obesity, such as cholesterol, blood pressure and blood sugar.

The key to success is perseverance. Set yourself realistic body weight goals and recognise that lifestyle change requires long-term vigilance of food intake and physical activity.

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