Increased weight loading reduces body weight and body fat in obese subjects - A proof of concept randomized clinical trial

Abstract

Background: Recently we provided evidence for a leptin-independent homeostatic regulation, the gravitostat, of body weight in rodents. The aim of the present translational proof of concept study was to test the gravitostat hypothesis in humans.

Methods: We conducted a randomized controlled single center trial (ClinicalTrial.gov number, NCT03672903), to evaluate the efficacy of artificially increased weight loading on body weight in subjects with mild obesity (BMI 30-35 kg/m²). Subjects were either treated with a heavy (=high load; 11% of body weight) or light (=low load; 1% of body weight) weight vest for eight hours per day for three weeks. The primary outcome was change in body weight. Secondary outcomes included change in body fat mass and fat-free mass as measured using bioelectrical impedance analysis.

Findings: In total 72 participants underwent randomization and 69 (36 high load and 33 low load) completed the study for the primary outcome. High load treatment resulted in a more pronounced relative body weight loss compared to low load treatment (mean difference -1.37%, 95% confidence interval (CI), -1.96 to -0.79; p = 1.5 × 10^-5). High load treatment reduced fat mass (-4.04%, 95% CI, -6,53 to -1.55; p = 1.9 × 10^-3) but not fat free mass (0.43%, 95% CI, -1.47 to 2.34; p = 0.65) compared to low load treatment.

Interpretation: Increased weight loading reduces body weight and fat mass in obese subjects in a similar way as previously shown in obese rodents. These findings demonstrate that there is weight loading dependent homeostatic regulation of body weight, the gravitostat, also in humans.

Funding: Funded by Jane and Dan Olsson (JADO) Foundation, the Torsten Söderberg Foundation, The Knut and Alice Wallenberg's Foundation and the Novo Nordisk Foundation.

Fig. 1

CONSORT Diagram describing enrolment and randomization. The 27 subjects with screening failure did not meet all inclusion criteria and/or did meet at least one of the exclusion criteria as described in Methods.

Fig. 2

Change in body weight, fat mass and fat free mass at 3 weeks vs baseline for all subjects who completed the study. Results are presented as least square means with 95% confidence intervals for all randomized subjects with body weight available both at baseline and at 3 weeks treated with light weight vest (Low load; n = 36) or heavy weight vest (High load, n = 33). The between group p-values (High load vs Low load) given within the figure are calculated using analysis of covariance (ANCOVA) adjusted for age, sex, baseline BMI, Vest exposure (h) and standing % with vest. *** = p<0.001 for within group comparison (Three weeks vs baseline) using Wilcoxon signed rank-sum test.