The Relation Between Adult Weight Gain, Adipocyte Volume And The Metabolic Profile At Middle Age

Purpose Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy. We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume. Methods Nuclear magnetic resonance-based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n=6 347, discovery) and Oxford Biobank (n=6 317, replication). Adult weight gain was calculated as the absolute difference between BMI at middle age and recalled BMI at age 20. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n=114) to estimate adipocyte volume. Results Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI 143 – 629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain. Main conclusions Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.

Omega-3 Polyunsaturated Fatty Acids Prevent Nonalcoholic Steatohepatitis (NASH) and Stimulate Adipogenesis

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells’ proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals’ body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.

Adipose Tissue Fibrosis: Mechanisms, Models, and Importance

Increases in adipocyte volume and tissue mass due to obesity can result in inflammation, further dysregulation in adipose tissue function, and eventually adipose tissue fibrosis. Like other fibrotic diseases, adipose tissue fibrosis is the accumulation and increased production of extracellular matrix (ECM) proteins. Adipose tissue fibrosis has been linked to decreased insulin sensitivity, poor bariatric surgery outcomes, and difficulty in weight loss. With the rising rates of obesity, it is important to create accurate models for adipose tissue fibrosis to gain mechanistic insights and develop targeted treatments. This article discusses recent research in modeling adipose tissue fibrosis using in vivo and in vitro (2D and 3D) methods with considerations for biomaterial selections. Additionally, this article outlines the importance of adipose tissue in treating other fibrotic diseases and methods used to detect and characterize adipose tissue fibrosis.

3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet

When administered to rats receiving a high-fat diet (HFD), 3,5-diiodo-L-thyronine (3,5-T2) [at a dose of 25 μg/100 g body weight (BW)] is known to increase energy expenditure and to prevent HFD-induced adiposity. Here, we investigated which cellular and molecular processes in visceral white adipose tissue (VAT) contributed to the beneficial effect of 3,5-T2 over time (between 1 day and 4 weeks following administration). 3,5-T2 programmed the adipocyte for lipolysis by rapidly inducing hormone sensitive lipase (HSL) phosphorylation at the protein kinase A-responsive site Ser563, accompanied with glycerol release at the 1-week time-point, contributing to the partial normalization of adipocyte volume with respect to control (N) animals. After two weeks, when the adipocyte volumes of HFD-3,5-T2 rats were completely normalized to those of the controls (N), 3,5-T2 consistently induced HSL phosphorylation at Ser563, indicative of a combined effect of 3,5-T2-induced adipose lipolysis and increasing non-adipose oxidative metabolism. VAT proteome analysis after 4 weeks of treatment revealed that 3,5-T2 significantly altered the proteomic profile of HFD rats and produced a marked pro-angiogenic action. This was associated with a reduced representation of proteins involved in lipid storage or related to response to oxidative stress, and a normalization of the levels of those involved in lipogenesis-associated mitochondrial function. In conclusion, the prevention of VAT mass-gain by 3,5-T2 occurred through different molecular pathways that, together with the previously reported stimulation of resting metabolism and liver fatty acid oxidation, are associated with an anti adipogenic/lipogenic potential and positively impact on tissue health.

Adipose tissues of MPC1± mice display altered lipid metabolism-related enzyme expression levels

Mitochondrial pyruvate carrier 1 (MPC1) is a component of the MPC1/MPC2 heterodimer that facilitates the transport of pyruvate into mitochondria. Pyruvate plays a central role in carbohydrate, fatty, and amino acid catabolism. The present study examined epididymal white adipose tissue (eWAT) and intrascapular brown adipose tissue (iBAT) from MPC1± mice following 24 weeks of feeding, which indicated low energy accumulation as evidenced by low body and eWAT weight and adipocyte volume. To characterize molecular changes in energy metabolism, we analyzed the transcriptomes of the adipose tissues using RNA-Sequencing (RNA-Seq). The results showed that the fatty acid oxidation pathway was activated and several genes involved in this pathway were upregulated. Furthermore, qPCR and western blotting indicated that numerous genes and proteins that participate in lipolysis were also upregulated. Based on these findings, we propose that the energy deficiency caused by reduced MPC1 activity can be alleviated by activating the lipolytic pathway.

Children whose diet contained olive oil had a lower likelihood of increasing their body mass index Z-score over 1 year

ObjectiveChanges in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils.Design and methodsThe study included 18 girls and 74 boys, all aged 13–166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later.ResultsThe likelihood that after 1 year the children would have increased their body mass index (BMI)Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08–0.63;P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06–0.61;P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04–0.52;P=0.003).ConclusionsDiets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.