👤 M Guevara-Cruz

An increased number of low-density lipoprotein particles (LDL-P) is a common feature of patients with Metabolic syndrome (MetS). Increasing the size of these particles is one of the primary therapeutic and dietary interventions goals. However, genetic variability, like single nucleotide polymorphisms (SNPs), modulate the response to dietary strategies. Therefore, we hypothesise that the presence of SNPs in genes associated with MetS may modulate the effect of a dietary intervention on the size of LDL-P. This was a before-and-after clinical study conducted with 146 participants with MetS. The participants underwent a lifestyle intervention for 10 weeks. At baseline the presence of SNPs associated with MetS were determined. Anthropometric, biochemical, hormonal parameters, and lipoprotein analysis were taken before and after the intervention. Results revealed that the common homozygous ATP-binding cassette transporter A1 (ABCA1) genotype was associated with a decreased LDL-C concentration. However, after adjusting for sex, age and baseline weight, polymorphisms in the fat mass and obesity-associated (FTO) gene, the peroxisome proliferator-activated receptor (PPARγ), and the apolipoprotein E (APOE) gene were associated with a better response to the intervention in terms of increasing LDL-P size. Our results revealed changes in LDL-P size associated with polymorphisms in the APOE, FTO and PPARγ genes in response to the dietary intervention. These results highlight the importance of genetic factors in personalized nutritional strategies aimed at improving cardiovascular risk in patients with MetS. NCT03611140, www. gov. Show less

Childhood obesity increases the risk of developing metabolic diseases in adulthood, since environmental stimuli during critical windows of development can impact on adult metabolic health. Studies demonstrating the effect of prepubertal diet on adult metabolic disease risk are still limited. We hypothesized that a prepubertal control diet (CD) protects the adult metabolic phenotype from diet-induced obesity (DIO), while a high-fat diet (HFD) would predispose to adult metabolic alterations. Sprague-Dawley male rats were fed either a CD or a HFD during the prepubertal period (day 30-40 of age) and subsequently a chronic HFD or CD, respectively, until adulthood (day 220 of age). As controls, rats aged 30 days were exclusively fed a CD or a HFD until adulthood. Body weight and composition, metabolic rate, biochemical and hormonal plasma measurements, hepatic gene expression and methylation and hydroxymethylation levels were analyzed at ages 30, 40 and 220 days. The prepubertal CD prevented fat mass accumulation, lean mass loss and metabolic inflexibility, showed lower insulin, leptin and cholesterol concentrations in adulthood despite the chronic HFD. Notably, the prepubertal CD led to higher hepatic Lxrα expression, lower hepatic global DNA methylation and higher hydroxymethylation in adulthood despite a chronic HFD. Conversely, a prepubertal HFD decreased adult metabolic flexibility, increased serum cholesterol, and decreased Lxrα expression and global DNA hydroxymethylation, while also increasing DNA methylation levels despite a chronic CD. In summary, a prepubertal CD protected the adult metabolic phenotype from high cholesterol concentrations associated with increased hepatic Lxrα expression and lower hepatic global DNA methylation in adulthood, despite exposure to a chronic HFD. Conversely, a prepubertal HFD altered the adult metabolic phenotype. Show less