Tissue remodelling and changes in macrophage polarisation occur in adipose tissue (AT) and skeletal muscle (SM) in response to nutrient availability in animals [1-4]. This study aimed to compare the effects of daily calorie restriction (CR) versus intermittent fasting (IF) on markers of AT and SM remodelling in women.
Women (N=75, 50.3±1.0y, BMI 32.4±0.5 kg/m2) were randomised to 1 of 3 groups for 8 weeks, and provided with foods at 70% (IF70 and CR70), or 100% (IF100) of energy requirements. CR70 participants consumed food daily, whereas IF participants ate breakfast, prior to initiating a 24-hour fast, for 3 non-consecutive days/week. Fasting bloods, subcutaneous abdominal AT and quadriceps muscle biopsies were obtained at baseline, and 8 weeks, after a 12-h overnight fast (all groups), and 24-h fast (IF groups). Markers of macrophages and extracellular matrix (ECM) were examined by qPCR.
We observed significant weight loss after 8 weeks, with greater weight loss in IF70 vs. CR70 and IF100 (P<0.05). Insulin sensitivity, assessed by HOMA-IR, was improved in IF70 and CR70 following a 12-h fast and in all groups following a 24-h fast, with greatest improvement in IF70 (P<0.05). Reductions in NEFAs were greater in IF70 vs. CR70 after a 12-h fast, whereas NEFAs increased after a 24-h fast in IF groups (P<0.05). In AT, CD40 expression (M1-macrophage marker) was increased following a 24-h fast in IF70 and MMP2 (involved in breakdown of ECM), was increased in CR70 and IF70 (P<0.05). In SM, CD163 (M2-macrophage) expression was increased after 12- and 24-h fasts in fasting groups (P<0.05).
Weight loss stimulated markers of ECM remodelling in AT. IF increased pro-inflammatory M1 macrophage in AT and anti-inflammatory M2 macrophages in muscle. We speculate this increase in macrophages may be an appropriate response to buffer increased lipolysis in response to severe energy deprivation.