Abstract
BackgroundSubjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW.MethodsTwenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels.ResultsAfter overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects (p ≤ 0.03) and increased with 36 h fasting in NBW subjects only (p ≤ 0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage (p ≤ 0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting (p = 0.04) and decreased more than threefold in both groups after 36 h fasting (p ≤ 0.0001).ConclusionsThis is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.
Highlights
Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects
This was shown in LEP and ADIPOQ promoters in subcutaneous adipose tissue (SAT) among NBW but not LBW subjects
We investigated whether DNA methylation and expression of LEP and ADIPOQ were affected by 36 h fasting, in subcutaneous adipose tissue (SAT) from young, healthy NBW and LBW men
Summary
Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. Being born with low birth weight (LBW) has been confirmed in several human studies to be associated with increased risk of developing insulin resistance and T2D in adult life [22,23,24]. In this regard, several studies have reported alterations of epigenetic patterns and plasticity in human tissues that are relevant to metabolic diseases in subjects born at term with a LBW compared to normal birth weight (NBW) subjects [6, 8, 9, 25]
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