Rodent Models for Metabolic Syndrome Research

Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent

DNA methylation in adipose tissue and metabolic syndrome

Epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence with the processes including DNA methylation, histone modifications and RNA-associated silencing [1,2]. Castellano-Castillo and colleagues have analysed the impact of metabolic syndrome on the global DNA methylation pattern and the DNA methylation of several genes in visceral adipose tissue [3]. They concluded that DNA methylation in adipose tissue of these patients is related to the aetiology of the syndrome. The role of DNA methylation in genes for adipogenesis, inflammation and lipid metabolism provides logical explanations for these changes in the development and progression of metabolic syndrome [3]

Tropical seaweeds improve cardiovascular and metabolic health of diet-induced obese and hypertensive rats

Seaweeds have been an important part of the diet of coastal populations in Asia possibly for millennia but only a few scattered coastal communities in Europe and the Americas have maintained these traditions (Mouritsen et al, 2019). Our studies have investigated the potential of two tropical seaweeds grown commercially in Asia, Sarconema and Caulerpa spp., as functional foods for the reversal of metabolic syndrome and possible mechanisms. Sarconema spp. are a source of carrageenans used as thickening and gelling agents in foods while Caulerpa spp. are consumed in South-East Asia as low-energy foods with high contents of vitamins and minerals. For our studies, male Wistar rats were divided into groups in a 16-week protocol: corn starch diet-fed rats (C); C rats supplemented with 5% dried seaweed for the last 8 weeks; high-carbohydrate, high-fat diet-fed rats (H); and H rats supplemented with 5% dried seaweed for the last 8 weeks. H rats developed obesity, hypertension, dyslipidaemia, glucose intolerance, fatty liver and increased left ventricular collagen deposition, infiltration of inflammatory cells and plasma liver enzyme activities. Seaweed supplementation decreased body weight, abdominal and liver fat, systolic blood pressure, plasma lipid concentrations, plasma activities of liver enzymes and collagen deposition. Further, seaweed supplementation modulated gut microbiota. Possible mechanisms for improved cardiovascular and metabolic health include a reduced infiltration of inflammatory cells into organs as well as an increased intake of fibre modulating gut microbiota composition

Rind from purple mangosteen (Garcinia mangostana) attenuates diet-induced physiological and metabolic changes in obese rats

The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms

Anthocyanins in chronic diseases : the power of purple

Anthocyanins are mainly purple-coloured phenolic compounds of plant origin that as secondary metabolites are important in plant survival. Understanding their health benefits in humans requires sourcing these unstable compounds in sufficient quantities at a reasonable cost, which has led to improved methods of extraction. Dark-coloured fruits, cereals and vegetables are current sources of these compounds. The range of potential sustainable sources is much larger and includes non-commercialised native plants from around the world and agri-waste containing anthocyanins. In the last 5 years, there have been significant advances in developing the therapeutic potential of anthocyanins in chronic human diseases. Anthocyanins exert their beneficial effects through improvements in gut microbiota, oxidative stress and inflammation, and modulation of neuropeptides such as insulin-like growth factor-1. Their health benefits in humans include reduced cognitive decline; protection of organs such as the liver, as well as the cardiovascular system, gastrointestinal tract and kidneys; improvements in bone health and obesity; and regulation of glucose and lipid metabolism. This review summarises some of the sources of anthocyanins and their mechanisms and benefits in the treatment of chronic human diseases

Nannochloropsis oceanica as a microalgal food intervention in diet-induced metabolic syndrome in rats

The microalgal genus Nannochloropsis has broad applicability to produce biofuels, animal feed supplements and other value-added products including proteins, carotenoids and lipids. This study investigated a potential role of N. oceanica in the reversal of metabolic syndrome. Male Wistar rats (n = 48) were divided into four groups in a 16-week protocol. Two groups were fed either corn starch or high-carbohydrate, high-fat diets (C and H, respectively) for the full 16 weeks. The other two groups received C and H diets for eight weeks and then received 5% freeze-dried N. oceanica in these diets for the final eight weeks (CN and HN, respectively) of the protocol. The H diet was high in fructose and sucrose, together with increased saturated and trans fats. H rats developed obesity, hypertension, dyslipidaemia, fatty liver disease and left ventricular fibrosis. N. oceanica increased lean mass in CN and HN rats, possibly due to the increased protein intake, and decreased fat mass in HN rats. Intervention with N. oceanica did not change cardiovascular, liver and metabolic parameters or gut structure. The relative abundance of Oxyphotobacteria in the gut microbiota was increased. N. oceanica may be an effective functional food against metabolic syndrome as a sustainable protein source

Caulerpa lentillifera (sea grapes) improves cardiovascular and metabolic health of rats with diet-induced metabolic syndrome

Caulerpa lentillifera (sea grapes) is widely consumed in South-East Asia as a low-energy food with high contents of vitamins and minerals. This study investigated dried sea grapes containing 16.6% insoluble fibre commercially produced in Vietnam as an intervention. We hypothesised that insoluble fibre is the primary metabolite that will reverse diet-induced metabolic syndrome. Male Wistar rats (n = 48) were randomly allocated to four groups in a 16 week protocol. Two groups were fed either corn starch (C) or high-carbohydrate, high-fat (H) diets for the full 16 weeks. The other two groups received C and H diets for eight weeks and then received C. lentillifera added to these diets for the final eight weeks (CCL and HCL, respectively). High carbohydrate, high-fat diet-fed rats developed obesity, hypertension, dyslipidaemia, fatty liver disease and increased left ventricular collagen deposition. C. lentillifera supplementation in HCL rats decreased body weight, systolic blood pressure, plasma concentrations of total cholesterol and non-esterified fatty acids, inflammatory cells in heart and liver, and visceral adiposity. The Firmicutes to Bacteroidetes ratio decreased in the gut microbiota of HCL rats. Therefore, C. lentillifera attenuated cardiovascular and metabolic symptoms of metabolic syndrome in rats, possibly by preventing infiltration of inflammatory cells together with modulating gut microbiota

Physiological and metabolic effects of yellow mangosteen (Garcinia dulcis) rind in rats with food-induced metabolic syndrome

Metabolic syndrome is a cluster of disorders that increase the risk of cardiovascular disease and diabetes. This study has investigated the responses to rind of yellow mangosteen (Garcinia dulcis), usually discarded as waste, in a rat model of human metabolic syndrome. The rind contains higher concentrations of phytochemicals (such as garcinol, morelloflavone and citric acid) than the pulp. Male Wistar rats aged 8–9 weeks were fed either corn starch diet or high-carbohydrate, high-fat diet for 16 weeks, which were supplemented with 5% freeze-dried G. dulcis fruit rind powder during the last 8 weeks. We characterised metabolic, cardiovascular, liver and gut microbiota parameters. High-carbohydrate, high-fat diet-fed rats developed abdominal obesity, hypertension, increased left ventricular diastolic stiffness, decreased glucose tolerance, fatty liver and reduced Bacteroidia with increased Clostridia in the colonic microbiota. G. dulcis fruit rind powder attenuated these changes, improved cardiovascular and liver structure and function, and attenuated changes in colonic microbiota. G. dulcis fruit rind powder may be effective in metabolic syndrome by appetite suppression, inhibition of inflammatory processes and increased fat metabolism, possibly related to changes in the colonic microbiota. Hence, we propose the use of G. dulcis fruit rind as a functional food to ameliorate symptoms of metabolic syndrome

Coffee pulp, a by-product of coffee production, modulates gut microbiota and improves metabolic syndrome in high-carbohydrate, high-fat diet-fed rats

Waste from food production can be re‐purposed as raw material for usable products to decrease industrial waste. Coffee pulp is 29% of the dry weight of coffee cherries and contains caf‐feine, chlorogenic acid, trigonelline, diterpenes and fibre. We investigated the attenuation of signs of metabolic syndrome induced by high‐carbohydrate, high‐fat diet in rats by dietary supplementation with 5% freeze‐dried coffee pulp for the final 8 weeks of a 16‐week protocol. Coffee pulp decreased body weight, feed efficiency and abdominal fat; normalised systolic blood pressure, left ventricular diastolic stiffness, and plasma concentrations of triglycerides and non‐esterified fatty acids; and improved glucose tolerance in rats fed high‐carbohydrate, high‐fat diet. Further, the gut microbiota was modulated with high‐carbohydrate, high‐fat diet and coffee pulp supplementation and 14 physiological parameters were correlated with the changes in bacterial community structures. This study suggested that coffee pulp, as a waste from the coffee industry, is useful as a functional food for improving obesity‐associated metabolic, cardiovascular and liver structure and function, and gut microbiota

Capsicum waste as a sustainable source of capsaicinoids for metabolic diseases

Capsaicinoids are pungent alkaloid compounds enriched with antioxidants, anti-microbial, anti-inflammatory, analgesics, anti-carcinogenic, anti-obesity and anti-diabetic properties. These compounds are primarily synthesised in the placenta of the fruit and then transported to other vegetative parts. Different varieties of capsicum and chillies contain different capsaicinoid concentrations. As capsicums and chillies are grown extensively throughout the world, their agricultural and horticultural production leads to significant amount of waste generation, in the form of fruits and plant biomass. Fruit wastes (placenta, seeds and unused fruits) and plant biowaste (stems and leaves) can serve as sources of capsaicinoids which can provide opportunities to extract these compounds for development of nutraceutical products using conventional or advanced extraction techniques. Capsaicin and dihydrocapsaicin are two most abundantly found pungent compounds. Considering the health benefits of capsaicinoids, these compounds can help in reducing metabolic disease complications. The development of an advanced encapsulation therapy of safe and clinically effective oral capsaicinoid/capsaicin formulation seem to require evaluation of strategies to address challenges related to the dosage, limited half-life and bioavailability, adverse effects and pungency, and the impacts of other ligands antagonising the major capsaicinoid receptor