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Habitual Physical Activity and Plasma Metabolomics Patterns Distinguish Individuals with Low vs. High Weight Loss during Controlled Energy Restriction

Background: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation.

Objective: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity.

Methods: Data were derived from a controlled feeding trial investigating the effect of 3–4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight–loss responders.

Results: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q2 = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (LR: 1.0 ± 0.6 kg/m2; HR: 3.3 ± 0.5 kg/m2P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P= 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01].

Conclusions: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures.


Alex’s Notes: There are incredible variations among people in response to dieting. Although much may be explained by genetics and dietary compliance, differences in metabolic and behavioral factors driving person-to-person variability in weight loss remain to be fully elaborated. As such, the current study used statistical modeling to identify determinants of weight loss that may play a role in this variation.

The data used in the current analysis was secondary data obtained from a previous study whereby 71 men and women (BMI 28-37; 20-45 years) completed a 15 week randomized controlled trial. The original goal was to assess the effect of 3-4 servings of dairy per day on weight loss when compared to low consumption. The participants were randomized to a low dairy (<1 serving) or high dairy (3-4 servings) group, but all persons were included for the current analysis independent of their original group. The first three weeks of the study were used to determine the maintenance caloric intake of each participant, after which the following 12 weeks induced a 500 kcal/day deficit. All foods were provided to the participants and compliance was excellent. No supplements were used and caffeine intake was kept constant. Moreover, physical activity was monitored with an accelerometer.

High-responder, low-responder

Total weight loss among all participants ranged from -0.5 to 14.9 kg, and was divided into tertiles whereby the “high-responders” lost >7.2kg and “low-responders” lost <5.2kg. Those in the middle were excluded from the current analysis to highlight the differences between high- and low-responders.

Compared with low-responders, high-responders had greater decreases over time in total body weight, BMI, total and percentage body fat, gynoid and android fat, and serum leptin concentrations, all of which can be explained simply by the greater amount of weight loss in these persons. Additionally, high- and low-responders did not differ by plasma insulin, glucose, triglycerides, or total cholesterol, but the total-to-HDL cholesterol ratio decreased in high-responders and increased in low-responders. Interestingly, at all time-points the high-responders also had a significantly lower respiratory exchange ratio (RER), indicative of greater fat oxidation, despite no differences in energy intake, caloric deficit, or resting energy expenditure.

Plasma stearic (18:0), oleic (18:1n–9), and palmitic (16:0) acids were significantly greater in high- than in low-responders, perhaps because of the greater fat loss and lower RER. Additionally, a metabolite of leucine catabolism was lower in high-responders, and threonic acid, succinic acid, citric acid, dodecanol, and dihydro-3-coumaric acid either increased or remained unchanged in high-responders, whereas they generally decreased in low-responders. In contrast, arachidic acid (20:0) was unchanged in high-responders and increased in low-responders.

Explaining it all with one simple lifestyle change

Regarding physical activity, the high-responders spent significantly less time being sedentary and more time being moderately active. The overall difference was a mere 3% of the day, or about 40 minutes, and yet this was enough to lead the authors to suspect it to be the driving force behind the high-responders’ apparent ability to better mobilize and utilize their fat stores.

In other words, physical activity results in a beneficial metabolic phenotype possibly through improved skeletal muscle fat oxidation, reduced leucine metabolism, and increased Kreb’s cycle dynamics.


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