Edible red seaweed Campylaephora hypnaeoides J. Agardh alleviates obesity and related metabolic disorders in mice by suppressing oxidative stress and inflammatory response

Abstract

Background: The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice.

Methods: Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells.

Results: Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, hyperglycemia, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-α, and interleukin-6 (IL-6) levels, while it decreased glutathione and superoxide dismutase. These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-α in macrophage RAW264.7 cells.

Conclusions: The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, hyperglycemia, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides.

Keywords: Campylaephora hypnaeoides J. Agardh; Diabetes; Hepatic steatosis; Inflammation; Obesity; Oxidative stress; Polysaccharide; Seaweed.

Fig. 1

The effects of C. hypnaeoides on body weight in C57BL/6J mice fed a high-fat diet. Normal, normal diet; HF, high-fat diet; HF + ChL, high-fat diet mixed with 2% C. hypnaeoides; HF + ChH, high-fat diet mixed with 6% C. hypnaeoides. Each value represents the mean ± SD (n = 12–13). Statistical significance: *p < 0.05 vs. HF group, ^##p < 0.01 versus Normal group

Fig. 2

The effects of C. hypnaeoides on the mass and morphology of white adipose tissue in C57BL/6J mice fed a high-fat diet. After the mice were sacrificed, the mass of the epididymal, retroperitoneal, and mesenteric white adipose tissue was determined (A). Adipose tissue was fixed and the section of epididymal adipose tissue was stained with hematoxylin and eosin (C). The average diameter of adipocytes was determined (B). Normal, normal diet; HF, high-fat diet; HF + ChL, high-fat diet mixed with 2% C. hypnaeoides; HF + ChH, high-fat diet mixed with 6% C. hypnaeoides. Each value represents the mean ± SD (n = 8). Statistical significance: *p < 0.05, **p < 0.01 versus HF group, ^##p < 0.01 versus Normal group. Scale bar = 100 μm

Fig. 3

The effects of C. hypnaeoides on the insulin resistance in C57BL/6J mice fed a high-fat diet. Insulin resistance was evaluated by a glucose tolerance test in the 12th week after high-fat diet ingestion (A), and the area under the curve (AUC) was calculated (B). Normal, normal diet; HF, high-fat diet; HF + ChL: high-fat diet mixed with 2% C. hypnaeoides; HF + ChH: high-fat diet mixed with 6% C. hypnaeoides. Each value represents the mean ± SD (n = 6–8). Statistical significance: *p < 0.05, **p < 0.01 versus HF group, ^##p < 0.01 versus Normal group

Fig. 4

The effects of C. hypnaeoides on the hepatic lipid accumulation in C57BL/6J mice fed a high-fat diet. A Liver weight, B Triglyceride content, C Representative gross morphology, D Histological sections of the liver. Normal, normal diet; HF, high-fat diet; HF + ChL, high-fat diet mixed with 2% C. hypnaeoides; HF + ChH, high-fat diet mixed with 6% C. hypnaeoides. Each value represents the mean ± SD (n = 6–8). Arrows indicate lipid droplets, and arrow heads indicate hepatocyte swelling. Statistical significance: *p < 0.05, **p < 0.01 versus HF group, ^##p < 0.01 versus Normal group. Scale bar = 100 μm

Fig. 5

The effects of C. hypnaeoides on the fecal weight and fecal components in C57BL/6J mice fed a high-fat diet. Feces samples were collected from each mouse after high-fat diet ingestion for 10 weeks, and the fecal weight was measured (A). The triglyceride (B) and polysaccharides (C) content were determined after extraction with isopropanol and distilled water, respectively. Normal, normal diet; HF, high-fat diet; HF + ChL, high-fat diet mixed with 2% C. hypnaeoides; HF + ChH, high-fat diet mixed with 6% C. hypnaeoides. Each value represents the mean ± SD (n = 7). Statistical significance: **p < 0.01 versus HF group, ^##p < 0.01 versus Normal group

Fig. 6

The effects of C. hypnaeoides polysaccharides and ethanol extract on the production of nitric oxide (A, C) and TNF-α (B, D) in RAW 264.7 cells. Each values represents the mean ± SD (n = 6). Statistical significance: **p < 0.01 versus LPS + Ch polysaccharides (0 μg/ml) or LPS + EtOH extract (0 μg/ml), ^##p < 0.01 versus Control