*3.3. Lipid Profile, Inflammation, and Heart Rate*

Lipid-associated risk for cardiovascular disease events is gradual and continuous. LDL carries cholesterol from the liver throughout the body and leaves excess on the endothelium of the arteries, causing atherosclerotic plaques to develop. Consequently, a surplus of LDL cholesterol is associated with an increased risk of cardiovascular events in patients both with and without type 2 diabetes [34]. Therefore, as a primary goal of therapy, target LDL cholesterol levels for adults with diabetes are <2.60 mmol/L [35]. In the present study, no effect was observed on lipid parameters. Our results are not in accordance with those of Shin et al. [36], who observed a decrease in total and LDL cholesterol following daily consumption of 144 mg of *Ecklonia cava* brown seaweed during 12 weeks among hypercholesterolemic subjects, nor with those of Iacoviello et al. [37] who reported a decrease in triglycerides after the consumption of a high dose (900 mg) of *Ascophyllum nodosum* extract over 6 weeks. The difference could be explained by the nature of the seaweed, the dose, and the duration of the trial. Further studies with higher doses of *Ascophyllum nodosum* and *Fucus vesiculosus* extract are suggested to assess the impact of its consumption on lipid profile among people at risk of type 2 diabetes.

Inflammation and oxidative stress may play a pivotal role in the pathophysiology of type 2 diabetes. The elevated inflammatory and oxidative biomarkers observed at the post-intervention stage could be explained by the chronic inflammation process that is implicated in diabetes. Among several inflammatory biomarkers, Il-6 has been shown to predict the development of type 2 diabetes, promoting the development of inflammation, insulin resistance, and β-cell dysfunction [38]. In the present study, our results indicate that the extract inhibited the increase in IL-6 observed in overweight/obese placebo subjects, thereby attenuating early pro-inflammatory response, and suggesting that consumption of the extract might have potential anti-inflammatory properties. In line with this result, it has already been shown that *Ascophyllum nodosum* extract can inhibit pro-inflammatory IL-6 gene expression in the porcine colon ex vivo and in vitro [39,40]. Phlorotannins are proposed as the main compounds in marine brown seaweeds associated with this effect. Indeed, as reported by Catarino et al. [41], phlorotannins can inhibit the expression of pro-inflammatory cytokines and interfering with transcriptional regulation. Furthermore, in the present study, variations in Il-6 were strongly and positively correlated with glycemia in the fasting state (*r* = 50, *p* = 0.001). Furthermore, in post-intervention, we observed trends between Il-6 and insulin resistance measured by HOMA-IR (*r* = 26, *p* = 0.07), and Il-6 and plasma insulin values at 120 min during OGTT (*r* = 0.24, *p* = 0.10). These results suggest that the inhibition of IL-6 increase could be a mechanism responsible for the observed effects of the brown seaweed extract on parameters related to glucose homeostasis. However, in the present study, hs-CRP was not affected by treatment; therefore, indicating no effect of brown seaweed extract on the pro-inflammatory late regulation process. Interestingly, a late anti-inflammatory response, characterized by a decrease in inflammatory biomarkers TNFα and hsCRP, was observed in an earlier 6-month study [27] investigating the metabolic and inflammatory effects of an extract of *Ascophyllum nodosum* and *Fucus vesiculosus* combined with chromium picolinate, therefore supporting the concept that the addition of chromium to brown seaweed extract might modulate inflammation differently [42].

Interestingly, heart rate is associated with inflammation [43] and plasma IL-6 concentrations [44]. We indeed observed a positive correlation between variations in heart rate and Il-6 (*r* = 0.29, *p* = 0.04). Therefore, the reduced heart rate seen in the brown seaweed group could be linked to the inhibition of increased pro-inflammatory marker Il-6. Interestingly, Jung et al. [45] previously observed that dieckol, a phlorotannin present in brown seaweed, can induce in vitro inhibition of cyclooxygenase 2 expression and prostaglandin E(2) production.
