Abstract
Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.
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Key Points
The key targets for obesity prevention and treatment interventions should be exercise and diet, which are two health-associated physiological regulators capable of activating AMP-activated protein kinase (AMPK), a common regulatory mechanism for inhibiting both cholesterol and fatty acid synthesis.
Previous research by this lab demonstrated that rats fed high soybean fiber gained more body weight (BW) and that flaxseed gum (flaxseed polysaccharide, FP) regulated gut microbiota and reduced BW and body fat. In this study, the authors sought to further elaborate the antiobesity mechanism of FP.
Insulin resistance commonly exists in patients with diabetes who often simultaneously suffer from obesity. In this study, no insulin resistance was found in group HFD, as the control diet (AIN-93M) but not the high fat diet (D12492) was supplied to them after the obesity model had been established. Conversely, rats fed an FP diet (group FPD) secreted as much insulin as the lean rats (rats fed D12450B during obesity model development and then AIN-93M for the rest of the trial), which indicates that FP was capable of recovering the insulin level and maintaining the normality of the blood glucose level. FP can lower BW by reducing body fat. Obesity is strongly linked with NAFLD, which is not only a chronic disease causing liver injury but also an emerging driving force in chronic kidney disease. At the end of the study, it is very possible that rats in group HFD had suffered from NAFLD, judging by the multiple lipid droplets in the liver as well as the histological status, but FP reduced the lipid droplets back to the normal level and relieved the abnormal state in the liver, thus showing a great potential to reverse the progress of NAFLD.
This is the first report that investigated the anti-inflammatory ability of FP. Since obesity and inflammation are closely related, the antiobesity effect of FP may be the cause and the result of inhibited inflammation. It is known that AMPK regulates lipid metabolism by mediating a series of proteins within the AMPK signaling pathway. Adiponectin, one of the upstream proteins of the AMPK signaling pathway, can stimulate AMPK expression. The current research displayed the increased level of adiponectin and elevated AMPK expression. FP-elevated APMK could inhibit the level of SREBP- which is a transcription factor that promotes the expression of multiple lipogenic enzymes, including FAS. It should be noted that only FP could remove leptin resistance and simultaneously activate the AMPK signaling pathway to enhance lipolysis and fatty acid oxidation and to suppress lipogenesis. This is also the first report describing the potential antiobesity mechanism of FP.