Identification of Mest/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions

Abstract

Food components with anti-obesity properties are commonly evaluated using mouse models of diet-induced obesity. The ability of these components to reduce or prevent white adipose tissue (WAT) accumulation is usually tested in feeding trials of several weeks duration in order to detect significant effects on fat mass expansion. Here, we aimed to identify early, predictive biomarkers for WAT expansion. We performed a 5-day high-fat diet (HFD) feeding trial with C57BL/6J mice using different established anti-obesity interventions: epigallocatechin gallate, replacing dietary lipids by n-3 PUFA, and increasing dietary protein. WAT gene expression was analyzed of genes known to be similarly affected by shortand long-term HFD. Gene expression of Leptin and Mest (mesoderm-specific transcript) was increased by HFD and normalized by all anti-obesity interventions. In a second experiment, translatability to whole blood-based expression data was assessed. Mice were challenged for 21 days with a HFD without or with simultaneous treatment with anti-obesity bioactives, hydroxytyrosol or resveratrol, and compared for parameters including Leptin and Mest expression in whole blood at day 5. While Leptin mRNA could not be detected in mouse whole blood, there was an induction of Mest mRNA by HFD which was suppressed by hydroxytyrosol. Moreover, Mest expression in whole blood at day 5 positively correlated with adiposity and negatively with lean body mass and the subcutaneous/visceral fat ratio at day 21. We conclude that gene expression of Leptin and Mest in WAT and of Mest in whole blood represent early, predictive markers of adipose tissue expansion of potential usefulness in nutritional studies and trials.Keywords Obesity Á Whole blood Á Mesoderm-specific transcript (Mest/Peg1) Á Epigallocatechin gallate (EGCG) Á n-3 PUFA Á High-protein diet Á Hydroxytyrosol Á Resveratrol

Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life

“…In fact, HFD‐induced adipocyte hypertrophy was readily apparent in the treated male mice, as illustrated in Figure B for RSV mice. Moreover, in accordance with these results, gene expression of Lep and Mest , which are markers of WAT expansion, was similarly induced by HFD feeding in control, RSV, and NR male mice (Figure C).…”

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

“…One gene of uncertain functional importance found in that study is SOX6 [SRY (sex determining region Y)-box 6]. Here, we describe the effects of SOX6 on adipogenesis and demonstrate putative molecular mechanisms by showing that SOX6 regulates the expression of key adipogenic regulators and synergizes with epigenetic pathways involving MEST (mesoderm specific transcript), which is known to be associated with adipocyte size (Takahashi et al, 2005) and adipose tissue expansion but with as yet unknown biochemical functions (Voigt et al, 2015). Epigenetic changes within the MEST promoter have previously been associated with maternal stress leading to adverse birth outcomes (Vidal et al, 2014).…”

C57BL/6J mice as a polygenic developmental model of diet-induced obesity

“…; Voigt et al. ), to be induced in response to a positive energy balance, not a high fat diet. Mice fed a HF when housed in the cold (4°) have a high energy expenditure that prevents the development of a positive energy balance.…”