Exercise reduced the formation of new adipocytes in the adipose tissue of mice in vivo

Abstract

Exercise has beneficial effects on metabolism and health. Although the skeletal muscle has been a primary focus, exercise also mediates robust adaptations in white adipose tissue. To determine if exercise affects in vivo adipocyte formation, fifty-two, sixteen-week-old C57BL/6J mice were allowed access to unlocked running wheels [Exercise (EX) group; n = 13 males, n = 13 females] or to locked wheels [Sedentary (SED) group; n = 13 males, n = 13 females] for 4-weeks. In vivo adipocyte formation was assessed by the incorporation of deuterium (2H) into the DNA of newly formed adipocytes in the inguinal and gonadal adipose depots. A two-way ANOVA revealed that exercise significantly decreased new adipocyte formation in the adipose tissue of mice in the EX group relative to the SED group (activity effect; P = 0.02). This reduction was observed in male and female mice (activity effect; P = 0.03). Independent analysis of the depots showed a significant reduction in adipocyte formation in the inguinal (P = 0.05) but not in the gonadal (P = 0.18) of the EX group. We report for the first time that exercise significantly reduced in vivo adipocyte formation in the adipose tissue of EX mice using a physiologic metabolic 2H2O-labeling protocol.

Fig 1. Study design schematic.

In vivo adipocyte formation was examined in fifty-two male (n = 26) and female (n = 26) C57BL/6J mice. Twelve-week old mice were fed a standard chow diet until 16 weeks of age. Mice were then switch to single housed cages with locked running wheels. After an adaptation period of one week, all were given a bolus injection of ²H₂O (35 ml/kg body weight 0.9% NaCl in 100% ²H₂O) and provided 8% ²H₂O drinking water and low-fat diet (10% fat). Body composition was measured by NMR at week 16 and week 20. Half of the mice were then allowed access to unlocked running wheels (EX group; n = 13 males, n = 13 females) or to wheels that remained locked to serve as sedentary controls (SED group; n = 13 males, n = 13 females) for 4-weeks.

Fig 2. Effects of exercise on wheel running kilometers and food intake in male and female mice.

Singly housed male and female mice were monitored for 4-weeks following a bolus injection of ²H₂O to achieve ~5% body water enrichment. Mice were provided ad libitum access to 8% ²H₂O drinking water (to maintain body water enrichment) and switched to low fat diet at start of the intervention. During the 4-week intervention period, half of the mice were allowed access to an unlocked running wheel (EX group; n = 13 males, n = 13 females), while the other mice had access to wheels that remained locked to serve as sedentary controls (SED group; n = 13 males, n = 13 females). Wheel running (2A) and food intake (2B-C) were measured weekly in male (n = 13) and female (n = 13) mice. g, grams; VWR, voluntary wheel running; EX, Exercise group; SED, Sedentary group. All data are presented as Mean ± SEM.

Fig 3. Changes in body weight and fat mass during the 4-week intervention period.

(A) Body weight was measured weekly in the mice during the study period. (B) NMR was performed to measure adipose tissue mass prior to the exercise period (baseline) and post-intervention. The change (Δ) in adipose tissue mass during the intervention period was calculated as ‘AT mass post-intervention–AT mass baseline’. n = 13/group. g, grams. All data are presented as Mean ± SEM.

Fig 4. New adipocyte formation is reduced in exercising mice.

New adipocyte formation was compared between SED and EX mice in the iWAT and gWAT (main effect for activity; p = 0.02) and in males and females (main effect for activity; p = 0.03). Additional independent pairwise analyses by depot (4A) and sex (4B) were conducted comparing new adipocyte formation in SED versus EX mice. n = 13/group. iWAT, inguinal white adipose tissue; gWAT, gonadal white adipose tissue; EX, exercise; SED, Sedentary. All data are presented as Mean ± SEM.