Seafood proteins in the prevention of the metabolic syndrome

Summary 200515 - Seafood proteins in the prevention of the metabolic syndrome - October 2015 At start of this project, we hypothesized that intake of lean seafood could prevent diet-induced obesity, improve glucose homeostasis and insulin-sensitivity, and prevent hyperlipidemia. The results obtained in the project are summarized below. Diet induced obesity In mice fed high fat diets, exchanging terrestrial meat with lean seafood as protein source generally led to lower diet-induced obesity (Tastesen 2014 AMAC & PlosOne; Holm submitted JNB, Jensen submitted Nutr & Metab). Parts of this weight-reducing effect was likely due to a somewhat lower energy intake in mice fed lean seafood diets (Tastesen 2014 AMAC, Holm submitted JNB). However, under conditions with equal energy intake, lean seafood ingestion still caused lower adiposity, possibly due to a higher spontaneous locomotor activity (Tastesen 2014 PlosOne). In mice fed high-fat, high-protein diets, cod as dietary protein source gave lower diet-induced obesity, as compared to chicken- or pork filets as dietary protein sources (Liisberg 2015 Adipocyte). Thus, in mice lean seafood intake generally led to reduced adiposity as compared to terrestrial meat intake. In contrast, from the randomized, controlled trial with healthy subjects, interventions with 60% of dietary protein from lean seafood or nonseafood sources for 4 weeks did not cause differences with regard to change in body mass or body composition between the dietary treatments (Aadland 2015 AJCN & submitted J Nutr). Therefore, lean seafood intake attenuated diet-induced obesity in high fat fed mice, but not in healthy humans consuming healthy and balanced diets. Glucose homeostasis and insulin-resistance In high fat fed mice, intake of lean seafood did not result in significant reduced blood glucose concentrations following an oral glucose challenge, as compared to intake of chicken filet (Tastesen 2014 AMAC, Holm submitted J Nutr Biochem). However, fasting insulin, a marker of insulin-sensitivity, tended to be reduced after lean seafood ingestion (Tastesen 2014 AMAC, Holm submitted J Nutr Biochem). Moreover, indices of hepatic insulin resistance, tended to be (Tastesen 2014 AMAC) or was (Holm submitted J Nutr Biochem) significantly improved after lean seafood intake as compared to after chicken filet intake in mice. In agreement with these notions, hepatic triacylglycerol, whose hepatic deposition is tightly associated with impaired insulin sensitivity, was higher after chicken filet intake in mice (Tastesen 2014 AMAC, Holm submitted J Nutr Biochem). In healthy subjects, postprandial C-peptide, an early marker of insulin-resistance, and postprandial lactate, a marker of altered intracellular glucose metabolism, was lower after 4 weeks of lean seafood intake, as compared to 4 weeks of nonseafood intake (Aadland submitted J Nutr). Moreover, postprandial very low-density lipoprotein (VLDL) concentration, normally reduced by insulin-mediated signaling, was reduced after the lean seafood intervention (Aadland 2015 AJCN). Based on the urinary metabolome (Schmedes submitted Mol Nutr Food Res), the lean-seafood intervention maintained mitochondrial activity, whereas the non-seafood intervention may have induced a higher protein catabolism, both of these findings could be associated with altered insulin function. Thus, both in mice and in healthy subject intake of lean seafood appeared to improve insulin sensitivity relative to dietary nonseafood ingestion. Hyperlipidemia and atherosclerosis In high fat fed mice, lean seafood as dietary protein source generally lowered plasma concentrations of triacylglycerol (TAG) and cholesterol, relative to intake of terrestrial meat protein sources, even though the differences not always reached statistical significance (Tastesen 2014 AMAC & PlosOne; Holm submitted JNB). Importantly, the atherosclerotic plaque burden was lower after feeding apolipoprotein E knockout (Apo E-/-) mice diets with lean seafood as compared to feeding mice with chicken filets as dietary protein sources (Jensen submitted Nutr & Metab). In healthy subjects, 4 weeks dietary intervention with lean seafood significantly reduced fasting and postprandial TAG and VLDL concentrations, and prevented an elevation in total cholesterol to high-density lipoprotein cholesterol ratio, as compared to the nonseafood intervention. Thus, both in high fat fed mice and in healthy humans, lean seafood as compared to nonseafood diets prevented hyperlipidemia. Furthermore, in Apo E-/- mice, lean seafood ingestion relieved the atherosclerotic burden in aorta relative to nonseafood ingestion, strongly suggestion a cardio protective function. Conclusions Intake of lean seafood based diets, as compared to nonseafood diets, improves postprandial glucose and lipid metabolism in a manner that may have impact on long-term development of insulin-resistance, type-2 diabetes and cardiovascular disease.

Hypothesis: Our hypothesis is that seafood protein sources rich in taurine and pantothenic acid can stimulate glutathione (GSH) synthesis and modulate bile-acid (BA) metabolism, and that this may induce intestinal release of glucagon-like peptide-1 (GLP-1 ) and fibroblast growth factor 15/19 (FGF15/19) to blood. We also hypothesize that the blood BA concentration can be modestly elevated in seafood protein consuming animals and subjects. Collectively, the metabolic pathways activated through the increased GSH, BA, GLP-1, FGF15/19 levels will reduce many of the pathological characteristics of the metabolic syndrome, such as insulin-resistance and hyperglycemia, dyslipidemia, atherosclerosis and abdominal obesity. We will screen different seafood protein so urces for their content of different nutrients, and based on their content of taurine and pantothenic acid, we will make a selection of seafood protein sources to be tested in experimental high-fat diets to mice. Control proteins will be casein and in som e experiments we might also use chicken filet protein as a second control protein. Initially, we will screen for the ability of 4-6 selected seafood proteins to prevent mice from developing abdominal obesity, plasma lipids, and plasma glucose and insulin levels. Next, we will test the ability of a mix of seafood proteins to improve postprandial blood lipids. Thirdly, we will test the ability of the same mix of seafood proteins to prevent development of insulin-resistance. Finally, we will test the abilit y of the seafood protein mixture to prevent development of atherosclerotic lesions. In these studies, we will use mice and cell-systems to elucidate underlying mechanisms. Based on the findings in mice and the cell-systems, we will run a human interventi on study with seafood proteins that will focus on postprandial lipid metabolism. In addition, grant applications will be written and submitted to Canadian Grant Agencies in order to conduct a Canadian human tr