Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice

Abstract

We recently demonstrated that palmitoleic acid (C16:1n7), a monounsaturated fatty acid, increases the metabolic and oxidative capacity of 3T3-L1 adipocytes. Herein, the effect of 16:1n7 supplementation on metabolic parameters on white adipose tissue (WAT) and liver of obese mice induced by a high-fat diet (HFD) was addressed by analyzing metabolic (dys)function and altered genes expression in adipose tissue, as well as liver and serum biochemistry analysis. For this purpose, mice were induced to obesity for 8 weeks, and from the 5th week, they received 16:1n7 (300 mg/kg per day) or water for 30 days, by gavage. Subcutaneous inguinal (ING) and epididymal (EPI) WAT were removed for analysis of metabolic, (anti)inflammatory, adipogenic, and thermogenic genes expression by real-time reverse transcriptase-polymerase chain reaction. Additionally, metabolic activities of isolated adipocytes, such as glucose uptake, lipogenesis (triacylglycerol esterification), β-oxidation, and lipolysis in ING adipocytes, were also assessed. Despite the higher fat intake, the HFD group showed lower food intake but higher body weight, increased glucose, significant dyslipidemia, and increased liver and adipose depot mass, accompanied by liver steatosis. The 16:1n7 supplementation slowed down the body mass gain and prevented the increase of lipids in the liver. HFD+n7 animals presented increased fatty acid oxidation and lipogenesis compared to control, but no effect was observed on lipolysis and glucose uptake in ING isolated adipocytes. Besides, 16:1n7 increased the content of the mRNA encoding FABP4, but partially prevented the expression of genes encoding ATGL, HSL, perilipin, lipin, C/EBP-α, PPAR-γ, C/EBP-β, CPT1, NRF1, TFAM, PRDM16, and nitric oxide synthase 2 in ING depot from HFD group of animals. Finally, HFD increased Mcp1 and Tnfα expression, and 16:1n7 promoted a more marked increase in it. In summary, the data show that palmitoleic acid promotes metabolic changes and partially prevents the increase in gene expression on adipocytes triggered by obesity, suggesting that HFD+n7 Cruz et al. Obesity, Adipocytes Metabolism and Palmitoleic Acid animals do not require the same magnitude of metabolic adaptation to cope with energy demand from the HFD. In the long term, the effects of 16:1n7 may be more evident and beneficial for the function/dysfunction of WAT from an obese organism, with relevant repercussions in the systemic metabolic homeostasis.

The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

“… 277 – 279 Give some examples, exercise training is the most effective strategy to prevent obesity and NAFLD, partially because β-aminoisobutyric acid secreted from myocytes promotes a switch from WAT to thermogenic phenotype and enhances fatty acid β-oxidation in hepatocytes both through the PPARα signaling pathway, and perhaps IL-6-induced upregulated thermogenesis also play a part in alleviating NAFLD. 280 , 281 In addition to aerobics, substantial strong evidence proved that some natural plant extracts could attenuate NAFLD by enhancing adipocytes browning and energy metabolism, such as the platycodon grandiflorus root (a Korean medicinal food, increases the expression of thermogenic genes like SIRT1, PPARα, PGC1A, and UCP1, which accompanied changes in fatty acid oxidation and energy expenditure), 282 pomegranate seed oil (increases the levels of thermogenic genes and hepatic HO-1, along with decreased inflammatory adipokines and hepatic fibrosis), 283 the Diospyros kaki fruit and Citrus unshiu mixture (activates fatty acid β-oxidation and thermogenesis, and inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element-binding protein 1 (SREBP-1) and SREBP-2 and its target genes), 284 palmitoleic acid (increase lipid metabolism in adipocytes), 285 cyanidin-3-O-β-glucoside (the most abundant monomer of anthocyanins, reduces adipokines secretion and lipid accumulation in HepG2 cells), 286 the ARPS (polysaccharides from Anoectochilus roxburghii (Wall.) Lindl, promotes fat thermogenesis via the AMPK/SIRT1/PGC1A signaling pathway).…”

Atractylodes chinensis Water Extract Ameliorates Obesity via Promotion of the SIRT1/AMPK Expression in High-Fat Diet-Induced Obese Mice

“…Increased lipogenesis and decreased β-oxidation lead to lipid accumulation in adipose cells [ 24 ]. To distinguish the molecular mechanisms of Ac on the reduction of eWAT mass, lipogenesis and fatty acid oxidation markers in eWAT were investigated by real-time PCR analysis.…”

High‐fat diet decreases H3K27ac in mice adipose‐derived stromal cells

“…Furthermore, the differences we found in Acly expression could be due to the different impact of the HFD on the subcutaneous and epididymal WAT. We have previously demonstrated that after an 8‐week HFD protocol, the leptin expression by subcutaneous adipocytes is increased more than 20 times, whereas in the epididymal adipocytes, this increase is less than 10 times [32], and studies have suggested that increased leptin signaling decreases Acly expression in WAT [33]. We cannot rule out the previously discussed effect of pooling cells from different animals in masking a more discrete difference in Acly expression in ASCs isolated from epididymal WAT of control and HFD‐fed animals.…”