Annette Bernhard:
The role of seafood nutrients and persistent organic pollutants in the development of metabolic diseases

Date: 15-02-2016    Supervisor: Karsten Kristiansen & Lise Madsen

Metabolic diseases are on the rise and pose a major threat to global public health. Consumption of fish and other seafood and associated long-chain omega-3 poly-unsaturated fatty acids (LC n3 PUFAs) are considered an integral part of a healthy diet, with documented beneficial effects on several cardiometabolic risk factors. However, consumption of fish and other seafood represent a major route for exposure to persistent organic pollutants (POPs), which have been implicated as a contributing risk factor to the development of metabolic diseases. Previous risk assessments addressing POP exposure through seafood consumption have mostly focused on the risks posed by POPs, and ignored the beneficial properties of seafood nutrients. While the potential of nutrients to modulate POP toxicity is increasingly recognised, it is largely uncharacterized with respect to dietary exposure.

The present thesis aimed to obtain essential knowledge required for balanced risk assessments of POP exposure through seafood consumption. Effects of seafood nutrients as well as toxic effects of dietary exposure to four of the most abundant POPs (polychlorinated biphenyl (PCB) -118, -138, -153 and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE)) and ɑhexabromocyclododecane (αHBCD), a POP of recent concern, were assessed in mice. In order to investigate potential nutritional modulation of POP toxicity, we compared exposure effects in combination with different diets, focusing on macronutrient composition, source of fat, and interaction with marine LC n3 PUFAs.

The results indicated that an effect of dietary background exposure to POPs on metabolic dysfunction cannot be excluded. However, the nutritional composition of the background diet appeared to be the main determinant for disease outcome and both accumulation and toxicity of the investigated POPs were highly dependent on the background diet. High levels of dietary carbohydrate determined the obesogenic potential of a high-fat diet and affected accumulation of POPs in adipose tissue. While a mixture of PCB-118, -138, -153 and p,p’-DDE did not impact body weight gain and insulin sensitivity, exposure to αHBCD interfered with lipid metabolism, likely affecting mitochondrial function. An effect of αHBCD exposure was evident at a level relevant to human exposure. Atherosclerotic plaque development was influenced by the dietary macronutrient composition, but not further affected by αHBCD exposure. Fish and fish oil as part of a high fat diet reduced hepatic lipid accumulation and improved insulin sensitivity. Furthermore, dietary fish oil reduced tissue accumulation of αHBCD in liver and adipose tissue, likely due to a combination of reducing levels of liver lipids and increasing metabolism of αHBCD. Beneficial effects of LC n3 PUFAs on liver lipids and insulin sensitivity appeared to be dependent on dietary n6 fatty acid levels, but may also be counteracted by the presence of αHBCD. Interestingly, an increased hepatic lipid load induced by elevated levels of omega-6 fatty acids in the diet appeared to have a cardioprotective effect.

The results of the present thesis highlight the impact of the dietary macronutrient composition in combination with POP exposure on the development of metabolic disease and highlights the importance of including diet into risk assessment strategies.