Fish-Derived Protein Hydrolysates Increase Insulin Sensitivity and Alter Intestinal Microbiome in High-Fat-Induced Obese Mice

Abstract

Obesity and type 2 diabetes are characterized by low-grade systemic inflammation and glucose intolerance, which can be partially controlled with nutritional interventions. Protein-containing nutritional supplements possess health-promoting benefits. Herein, we examined the effect of dietary supplementation with protein hydrolysates derived from fish sidestreams on obesity and diabetes, utilizing a mouse model of High-Fat Diet-induced obesity and type 2 diabetes. We examined the effect of protein hydrolysates from salmon and mackerel backbone (HSB and HMB, respectively), salmon and mackerel heads (HSH and HMH, respectively), and fish collagen. The results showed that none of the dietary supplements affected weight gain, but HSH partially suppressed glucose intolerance, while HMB and HMH suppressed leptin increase in the adipose tissue. We further analyzed the gut microbiome, which contributes to the metabolic disease implicated in the development of type 2 diabetes, and found that supplementation with selected protein hydrolysates resulted in distinct changes in gut microbiome composition. The most prominent changes occurred when the diet was supplemented with fish collagen since it increased the abundance of beneficial bacteria and restricted the presence of harmful ones. Overall, the results suggest that protein hydrolysates derived from fish sidestreams can be utilized as dietary supplements with significant health benefits in the context of type 2 diabetes and diet-induced changes in the gut microbiome.

Keywords: diabetes; fish; microbiome; obesity; protein hydrolysates.

Figure 1

Monitoring the effect of fish-derived hydrolysates in high-fat diet-induced insulin resistance. (A–F) Mice were fed with the indicated nutritional supplements and then subjected to a glucose tolerance test. Black color indicates the group of mice consuming the lean diet, and red color indicates the group of mice consuming the high-fat diet used as control. Graphs represent mean ± SEM. A 2-way ANOVA test was performed. ** p < 0.01.

Figure 2

The effect of fish-derived hydrolysates in weight accumulation during a high-fat diet (A–F). Black color indicates the group of mice consuming the lean diet, and red color indicates the group of mice consuming the high-fat diet used as control. Graphs represent mean ± SEM. A 2-way ANOVA test was performed. No statistical significance was observed.

Figure 3

The effect of fish-derived hydrolysates in abdominal fat accumulation (A), Leptin gene expression (B), and urine pH (C) during a high-fat diet. A Mann–Whitney t-test was performed. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 4

The effect of fish-derived protein hydrolysates on intestinal bacterial diversity. (A) PCoA and (B) Alpha Diversity analysis.

Figure 5

The effect of fish-derived dietary supplements on gut microbiome top genera composition. (A) Normalized bar plots of genera abundances (%) based on the identified OTUs; (B) Boxplots representing the abundance of different genera following diet supplementation. Mann–Whitney t-test was performed. * p < 0.05, ** p < 0.01.