Flight and Fight Can Be Key to Weight Loss

Nora E. Straznicky, PhD, MPH, from the Baker IDI Heart & Diabetes Institute in Melbourne, and colleagues stated that, "Weight loss in a cohort of 42 previously untreated patients was independently predicted by baseline resting muscle sympathetic nerve burst incidence (r=0.38; P=0.019)." This accounted for 14.3% of the variance after adjustment for age and body weight at baseline.

According to the article, the group that lost weight successfully had higher sympathetic nerve burst frequency and incidence (17% and 25% respectively) when compared with those who were weight loss resistant. They also had higher systolic blood pressures (P<0.05 for all).

Although weight loss is advocated as a first-line treatment for obesity, there remains considerable variation in how well patients do at losing weight, the authors noted. "Beyond dietary adherence and the effects of diet composition per se are biological determinants, encompassing genetic, hormonal, metabolic, and neuroadrenergic factors that may significantly modulate the weight loss response."

Although one of these components -- the sympathetic nervous system -- plays a vital role in metabolic regulation, previously published studies on the subject used either venous norepinephrine level or indirect methods to evaluate sympathetic activity, "which are suboptimal in terms of reproducibility and sensitivity when compared to more direct measures of sympathetic nerve firing rate," they wrote.

Therefore, the investigators began the current study using microneurography to look at the relationship between resting muscle sympathetic nerve activity, as well as sympathetic responsiveness, to weight loss. They used microneurography because it is "the only clinical method that directly quantifies central sympathetic outflow, measured as efferent post-ganglionic sympathetic nerve activity directed to skeletal muscle vasculature."

A total of 42 obese or overweight individuals between 45 and 69 years old who met the Adult Treatment Panel III criteria for metabolic syndrome were enrolled. A modification of Dietary Approaches to Treat Hypertension (DASH) was used as the diet prescription for the study. Participants were assessed twice (baseline and 12 weeks) with various blood and urine tests. They also were weighed and waist circumference measurements were taken.

Measurements of resting muscle sympathetic nerve activity were recorded using microneurography to directly quantify central sympathetic outflow. "Successful weight loss" was defined as a greater than 5.0% reduction in the baseline weight.

A subgroup of 22 patients was tested for dynamic response following a standard 75-g oral glucose tolerance test. Blood sampling was done at 0, 30, 60, 90, and 120 minutes from glucose administration. Whole-body insulin resistance also was calculated from these results.

In the second cohort, those exhibiting weight loss resistance had a blunted sympathetic response when given the oral glucose as compared with those with successful weight loss results (time x group interaction P=0.004). Muscle sympathetic burst activity decreased at all recorded times during the glucose tolerance test. Absolute changes in the muscle sympathetic nerve activity at 60 and 90 minutes following glucose were positively associated with weight loss actually obtained (r=0.53, P=0.04, r=0.78, P=0.002, respectively).

Using regression analysis, the maximum increment in muscle sympathetic nerve activity (MSNA) during the glucose tolerance test and increase in calf blood flow at 90 minutes were significant independent predictors of weight loss. After adjustment for age and baseline body weight, the MSNA change alone explained 45% of weight loss variance, while the changes in MSNA and calf blood flow together explained 62%, the investigators reported.

"Our findings have two broad clinical implications: firstly, the potential identification of individuals who will benefit most from lifestyle intervention and secondly, the use of therapeutic interventions to enhance post-prandial sympathetic and thermogenic responses," wrote the authors.

• Note that this study conducted over a 12-week period.
• Resting muscle sympathetic nerve activity and sympathetic nerve activity following an oral glucose challenge both independently predicted successful weight loss in 42 previously untreated overweight and obese individuals.

Straznicky NE, et al "Baseline sympathetic nervous system activity predicts dietary weight loss in obese metabolic syndrome subjects J Clin Endocrinol Metab 2011; DOI:10.1210/jc.2011-2320.