Australasian Science Magazine

The sympathetic nervous system subconsciously regulates blood pressure, metabolism, digestion, respiration and body temperature.

By Nora Straznicky & Elisabeth Lambert

Individuals vary widely in their ability to lose weight, with new evidence suggesting that up to 45% of the variability in weight loss is caused by individual differences in subconscious nerve activity.

Sixty per cent of adult Australians are either overweight or obese, and thus at increased risk of serious diseases such as type 2 diabetes, heart disease and cancer. On both individual and societal levels, excess body weight has far-reaching ramifications on quality of life, life expectancy and healthcare costs, making it a modern public health challenge.

Obesity is caused by a complex combination of lifestyle, environmental and biological factors. Changes in the global food system, which is producing more processed, calorie-dense foods, increasingly time-poor lifestyles and the advent of the computer age has led to an imbalance between food consumption and energy expenditure through physical exercise.

Beyond these modifiable factors are others that we can’t control, with our biology and genetic make-up contributing at least 40% to our bodyweight and shape. Our biology also includes hormonal, metabolic and nervous system factors that may play an important role not only in the development of obesity but also in the pursuit to lose weight.

Weight reduction through calorie restriction is not always successful, and there is considerable variation in the weight loss achieved by different people. Beyond behavioural factors such as dietary compliance and exercise level, and treatment factors such as diet composition, length of treatment and absence or presence of social support, are a range of recognised biological predictors. For example, younger age, heavier baseline weight, higher resting metabolic rate and levels of thyroid hormone are associated with a better weight loss response.

A recent study conducted by our research group at the Baker IDI Heart and Diabetes Institute has, for the first time, examined how a person’s nerve activity may influence dietary weight loss.

How Are Nerves Involved in Weight Loss?
The sympathetic nervous system is widely distributed throughout the body, and subconsciously regulates our internal environment via effects on blood pressure, metabolism, digestion, respiration and body temperature. The sympathetic system is continuously active, and the degree of activity varies from moment to moment and from organ to organ in adjustment to a constantly changing environment. Key metabolic functions under its control that relate to energy balance and bodyweight regulation include:
• resting metabolic rate (i.e. how much energy we burn during sleep and rest), which typically accounts for 60–70% of daily energy expenditure;
• the thermic effect of food, which is the increase in energy expenditure that occurs after food consumption and represents approximately 10% of daily energy expenditure;
• fat oxidation (i.e. the breakdown of fat tissue during fasting, weight loss and exercise); and
• exercise-related energy expenditure, which includes physical activity and spontaneous activity such as fidgeting.

Our study examined the relationship between baseline sympathetic nervous system activity and subsequent weight loss in a group of 42 middle-aged obese individuals on a 12-week low calorie diet. Nerve activity was measured by microneurography, which involves the insertion of microelectrodes into nerve fibre bundles in the lower leg. Electrical activity, representing sympathetic nervous impulses travelling from the brain to blood vessels within skeletal muscle, was recorded after an overnight fast and for 2 hours after a 75 gram sugar drink.

Figure 1 is an example of a neurogram obtained at rest under fasting conditions. It shows sympathetic bursts or nervous discharges that vary in both amplitude (strength) and frequency. These are manually counted and expressed as the number of bursts per minute and the number of bursts per 100 heartbeats.

Skeletal muscle is an important site for metabolic heat production, accounting for about 22% of resting metabolic rate and up to 50% of the thermic effect of food. Therefore, measurement of sympathetic activity directed to this region is of particular relevance for delineating the cross-talk between the nervous system and metabolism.

Study Findings
Our study found that successful weight losers, who lost an average of 9 kg after 12-weeks of dieting, had higher resting nerve activity at the start of the program compared with weight loss-resistant individuals who lost an average of only 3 kg. Sympathetic burst incidence in the two groups averaged 64 and 51 bursts per 100 heartbeats, respectively. This indicates that resting sympathetic nerve activity was 25% higher among successful weight losers.

Moreover, successful weight losers had large increases in nerve activity after consuming the carbohydrate test meal, whereas the responses were minimal in weight loss-resistant subjects. After adjusting for potential confounding factors such as age and baseline body weight, resting nerve activity explained 14% of the variability in the weight loss response. Nerve activity after the test meal was an even stronger weight loss determinant, explaining 45% of the variability.

The study findings, which were published in the Journal of Clinical Endocrinology & Metabolism in February, highlight the importance of biological determinants in weight loss success, and suggest that sympathetic nerve activity contributes significantly to metabolic efficiency.

Our interpretation of the data is that individuals who are able to mount a large sympathetic response to food intake are better able to dissipate the calories that they have consumed as heat. Previous studies conducted in respiratory chambers, which permit accurate assessments of daily energy expenditure, show that higher sympathetic nerve activity confers greater 24-hour energy expenditure and favours fat oxidation.

What Are the Implications of This Study?
These findings provide the potential to:
• identify individuals who are most likely to succeed in weight loss endeavours; and
• develop weight loss treatments that stimulate this specific nervous activity.

While microneurography is a highly specialised technique that is limited to the realms of research laboratories, more accessible measures of nerve activity are available to the wider community. For example, the main chemical released from sympathetic nerves is noradrenaline, and blood levels of this hormone in the fasting state and in response to food intake could be used as an index of sympathetic activity.

Over the past decades, much effort has focused on the development of anti-obesity drugs that enhance weight loss, and the sympathetic nervous system has been a logical target. The ideal drug in this regard would be one that selectively stimulates metabolic efficiency (resting metabolic rate, dissipation of calories after food intake and the breakdown of fat tissue) without unwanted side-effects. Unfortunately, because of the widespread distribution of the sympathetic nervous system within the body, any drug that stimulates this nerve activity often has effects on multiple organs and body functions. Unwanted side-effects of such drugs may include an increase in heart rate and blood pressure, insomnia, dry mouth and constipation, and these limit their long-term use.

Several ongoing trials are currently testing the long-term effectiveness and safety of drug combinations that include a component acting on the sympathetic nervous system.

What If You Are Weight Loss-Resistant?
The good news is that moderate-intensity exercise training has beneficial effects on the thermic effect of food. Therefore, regular brisk walking, swimming or bike-riding may help to facilitate greater weight loss.

It is also important to emphasise that even modest weight loss favourably influences the risk factors associated with obesity (cholesterol profile, blood pressure, blood sugar level). The key to success is perseverance, setting realistic bodyweight goals and recognising that lifestyle change requires long-term commitment, involving vigilance to both food intake and physical activity.

Future Research Directions
It is important to elucidate why some individuals have an impaired sympathetic response to food intake. It is likely that multiple mechanisms are involved, including hormonal, vascular and genetic factors. Insulin – the hormone released by the pancreas after food intake – is one of the main mediators of the sympathetic response. Our group and others have demonstrated that obese individuals who are insulin-resistant have blunted sympathetic nervous responses to test meals compared with obese individuals who are insulin-sensitive. There is evidence to suggest that insulin transport to the brain as well as insulin signalling is impaired in insulin-resistant states. Therefore, targeting insulin resistance through lifestyle interventions (e.g. weight loss and exercise) or drug treatment may offer a means to improve metabolic efficiency.

Preliminary trials of intranasal insulin, which provides a means of delivering insulin directly to the brain, show that it enhances the thermic effect of food. Other hormones, such as the stress hormone cortisol, may also modify insulin action and sympathetic activity. Its role in weight management requires further research. The influence of genetic factors, particularly in relation to the noradrenaline receptor, is also highly relevant to changes in bodyweight and body composition during weight loss.

Losing weight is challenging for many people and not simply a matter of willpower. Our study highlights that subconscious nervous system activity can have a significant bearing on weight loss success.