Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions

Abstract

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in adipose tissue. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor’s niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Astaxanthin Supplemented with High-Intensity Functional Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity

“…Changes in inflammatory conditions may be another pathway through which astaxanthin can improve metabolic changes induced by obesity, as astaxanthin inhibits the activation of the transcriptional factor of NF-κB to reduce the actions of pro-inflammatory cytokines [ 55 ]. Additionally, astaxanthin reduces the infiltration of inflammatory M1 macrophages into hypertrophied adipocytes, which mitigates the release of pro-inflammatory cytokines by macrophages and reduces the release of free fatty acids into circulation and improves insulin sensitivity [ 56 , 57 ]. Astaxanthin accelerates fatty acid oxidation during physical exercise [ 29 , 58 ].…”

Role of carotenoids in adipose tissue through the AMPK-mediated pathway

“…[27][28][29] A recent systematic review and meta-analysis pointed out that astaxanthin supplementation may improve inflammatory and oxidative stress serum markers in humans with type 2 diabetes. 30 Similarly, in animals fed with obesogenic diets and supplemented with low doses of astaxanthin for a long time, it attenuated pro-inflammatory macrophage infiltration (M1 type) in WAT, 31 and also exerted antioxidant effects by reducing the gene expression of heme oxygenase 1 (Hmox-1) and upregulating catalase in WAT, 32 and promoted epigenetic modulation by increasing sirtuin 3 (Sirt3) expression in WATa histone deacetylase that protects against mitochondria damage. 33 These antioxidant activities of astaxanthin may have also contributed to the partial reduction of inflammation.…”

“…33 These antioxidant activities of astaxanthin may have also contributed to the partial reduction of inflammation. 32 Fucoxanthin supplementation (0.2%) reduced macrophage infiltration and the expression of pro-inflammatory cytokines, such as monocyte chemoattractant protein-1 (MCP-1), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the WAT of diabetic and obese mice after 4 weeks of treatment. 34 Treatment with lycopene (0.03%) attenuated adipocyte hypertrophy and inflammation by downregulating TNF-α and IL-6 gene expressions and increasing the anti-inflammatory cytokine interleukin-10 (IL-10) in mice for 10 weeks of treatment.…”

“…37 In addition, the pro-inflammatory scenario is accompanied by the WAT expansion, which increases leptin and reduces adiponectin secretion, consequently, contributing to insulin resistance development. 32,38 Interestingly, astaxanthin contributes to healthy WAT expansion and reduces hypoxia induced by a HFD. 32 While lycopene reduced leptin in epididymal WAT; 35,39 astaxanthin and fucoxanthin contributed to the improvement of insulin sensitivity by increasing mRNA adiponectin expression in the WAT of obese rats and mice 32,40 and β-carotene in the adipocyte cell line.…”

Effect of Standardized Hydrangea serrata (Thunb.) Ser. Leaves Extract on Body Weight and Body Fat Reduction in Overweight or Obese Humans: A Randomized Double-Blind Placebo-Controlled Study

“…Epigallocatechin-3-gallate from green tea has the potential to increase fat oxidation and thermogenesis [ 10 , 11 ]. Moreover, astaxanthin, a marine carotenoid that possesses antioxidant activity, prevented the pathological remodeling of adipose tissue and stimulated mitochondrial biogenesis in muscle [ 12 , 13 ].…”