Potential of algae extracts for the attenuation of diet-induced metabolic syndrome

Metabolic syndrome is the clustering of multiple symptoms that directly increase the risk of developing cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease. It is estimated that one quarter of the world’s adult population has metabolic syndrome and rates of obesity have doubled in 70 countries between 1980 and 2015. Inducing weight loss and improving cardiometabolic health using food-based products is an attractive alternative to pharmaceutical treatment, as they are generally cheaper to produce and do not possess serious side effects. Edible algae have been consumed for thousands of years and remain a staple of the Japanese diet in particular to this day. Despite this, algae are rarely used as a health or food resource in Australia even though many species of algae are abundant along Australian coasts. Identifying the health benefits of Queensland-grown algae could lead to the development of high-value products to improve human health. The purpose of this PhD project was to determine whether extracts from three different algal species grown in north Queensland can attenuate diet-induced metabolic syndrome in rats. The advantages of rats in biomedical research are their anatomical and physiological similarities to humans, short lifespan, and ease of maintenance that allows for the testing of nutraceutical and pharmaceutical treatments in a pre-clinical trial (Hashway & Wilding 2020). This can help to determine whether a costly clinical trial is worth attempting, and guide dose selection and timing. The algal extracts of interest to this thesis included a highly sulphated soluble fibre known as ulvan, and two different carotenoid pigments called astaxanthin and fucoxanthin. To test the efficacy and safety of these algal extracts, a rat model using a validated high-carbohydrate, high-fat diet was used to mimic the human obesogenic diet. This obesogenic diet is characterised by an increased intake of saturated fat and simple carbohydrates and is linked to the development of obesity and the other symptoms of metabolic syndrome including high blood pressure, glucose intolerance, dyslipidaemia and fatty liver. Young, male Wistar rats were fed with the high-carbohydrate, high-fat diet for 16 weeks and a corn-starch-based diet was used to induce a lean control. The algal extracts were introduced into both of these diets at the 8-week mark using a low and a high dose to assess whether they could reverse or prevent further development of the symptoms of metabolic syndrome. Chapter 1 is a literature review of the characteristics of algae that highlight their potential for commercial success whilst simultaneously benefiting the environment. Furthermore, the therapeutic potential of the major algal extracts is explored. Chapter 2 is the description of the materials and methods used for the animal studies and analysis. Chapter 3 demonstrated that ulvan extracted from Ulva ohnoi slowed the progression of obesity by lowering body weight gain by 33% and fat mass gain by 36 - 45%, and through decreasing overall fat deposition in the liver. This anti-obesity effect was correlated with gut microbiome changes and a 25% reduction in feed efficiency. The Firmicutes/Bacteroidetes ratio was reduced from 64 to 11, and in particular Alistipes spp. and Prevotella spp. were increased in abundance. Chapter 4 investigated fucoxanthin extracted from Phaeodactylum tricornutum and demonstrated a normalisation of systolic blood pressure matching the corn-starch control (20 mm Hg reduction) and reduced fat deposition in the liver. While there were beneficial changes to serum lipids, including a 42% reduction to triglycerides and a doubling of high-density lipoprotein cholesterol, there was also a 117% elevation of low-density lipoprotein that increases the risk of cardiovascular disease. Chapter 5 discusses the response of obese rats to astaxanthin. It was found that a comparatively low dose of 1.2 mg/kg body weight/day was not effective in attenuating metabolic syndrome apart from a 34% reduction to serum triglycerides. This dose was selected based on the success of clinical trials testing a dose of 12 mg/day in humans, which is an equivalent dose to the one chosen for this study using the Reagan-Shaw formula for dose conversion. Overall, the animal studies conducted found that tropical Australian algae extracts, particularly ulvan and fucoxanthin, have potential for the treatment of metabolic syndrome. While astaxanthin has shown success in previous human and animal studies, it is likely that the dose used in this thesis was too low to produce an effect. Further work is needed to test these algal extracts in clinical studies to determine whether these health benefits can be translated to humans. A major challenge in translation is the high variability in algae biomass content and even the structure of algae extracts such as ulvan, in response to environmental variability and extraction technique. It is important that these factors are considered and reported on when designing future studies