Effects of low doses of fish and milk proteins on glucose regulation and markers of insulin sensitivity in overweight adults: a randomised, double blind study.

PURPOSE: To examine whether supplementation with low doses of fish or milk proteins would affect glucose regulation and circulating lipid concentrations in overweight healthy adults. METHODS: Ninety-three overweight adults were assigned to receive 2.5 g protein/day from herring (HER), salmon (SAL), cod (COD) or milk (CAS, a casein-whey mixture as positive control) as tablets for 8 weeks. RESULTS: Seventy-seven participants were included in the analyses. HER and SAL did not affect glucose and insulin concentrations. COD significantly reduced within-group changes in 90 and 120 min postprandial glucose concentrations but changes were not different from HER and SAL groups. CAS supplementation significantly reduced the area under the curve for glucose concentrations (- 7%), especially when compared to SAL group, and reduced postprandial insulin c-peptide concentration (- 23%). Reductions in acetoacetate (- 24%) and ß-hydroxybutyrate (- 29%) serum concentrations in HER group were more prominent compared to SAL and COD groups, with no differences between fish protein groups for α-hydroxybutyrate. Serum concentrations of α-hydroxybutyrate (- 23%), acetoacetate (- 39%) and ß-hydroxybutyrate (- 40%) were significantly reduced within CAS group, and the decreases were significantly more pronounced when compared to SAL group. Serum lipid concentrations were not altered in any of the intervention groups. CONCLUSION: Findings indicate that 2.5 g/day of proteins from fish or milk may be sufficient to improve glucose regulation in overweight adults. The effects were most pronounced after supplementation with proteins from cod, herring and milk, whereas salmon protein did not affect any of the measurements related to glucose regulation. CLINICAL TRAIL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT01641055.

Dietary intake of cod protein beneficially affects concentrations of urinary markers of kidney function and results in lower urinary loss of amino acids in obese Zucker fa/fa rats.

Obesity increases the risk for developing kidney disease, and protection of kidneys through changes in diet should be investigated. Fish intake has been associated with reduced risk of developing kidney disease; therefore, we wanted to investigate whether cod protein intake could prevent or delay the development of kidney damage in an obese rat model that spontaneously develops proteinuria and focal segmental glomerulosclerosis. The aim of the study was to investigate any effects of cod protein intake on established markers of kidney function, amino acid composition, protein utilisation and growth in obese Zucker fa/fa rats in the early stage of decreased renal function. Male obese Zucker fa/fa rats (HsdOla:Zucker-Lepr) were fed cod muscle proteins in an amount corresponding to 25 % of dietary protein, with the remaining protein from a casein/whey mixture (COD diet). A control group was fed a diet with a casein/whey mixture as the only protein source (CAS diet). The intervention started when rats were 9-10 weeks old, and the rats were fed these diets for 4 weeks. At the end of the study, rats fed the COD diet had lower urine concentration of cystatin C, T-cell immunoglobulin mucin-1 (TIM-1), amino acids, carbamide, uric acid and ammonium and higher concentrations of creatine, trimethylamine N-oxide, 1-methylhistidine and 3-methylhistidine, lower kidney concentration of TIM-1 and showed better growth when compared with the CAS group. To conclude, cod protein may have the potential to delay the development of kidney damage in young obese Zucker rats and to improve protein utilisation and growth.

Hydrolyzed proteins from herring and salmon rest raw material contain peptide motifs with angiotensin-I converting enzyme inhibitors and resulted in lower urine concentrations of protein, cystatin C and glucose when fed to obese Zucker fa/fa rats.

The use of angiotensin-I converting enzyme (ACE) inhibitors is a common strategy for treating kidney disease. Several amino acid sequences with ACE inhibiting activity are identified in filet and rest raw material from various species of fish, and fish protein hydrolysates could be of interest for possible treatment or prevention of kidney disease. Therefore, we hypothesized that protein hydrolysates from rest raw material from herring and salmon contained ACE inhibiting motifs, and could beneficially affect typical markers for kidney function in an obesity rat model prone to developing renal failure. We identified 81 and 49 peptide sequences with known ACE inhibiting activity in herring and salmon protein hydrolysates from rest raw material, respectively. To investigate the effects of fish protein hydrolysates on markers of kidney function, obese Zucker fa/fa rats consumed diets with 25% of protein from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material and 75% of protein from casein/whey, or 100% protein from casein/whey (CAS) for 4 weeks. Rats fed HER or SAL diets had lower urine concentrations (relative to creatinine) of protein, cystatin C and glucose when compared to rats fed CAS diets, with no differences between groups for serum concentrations of protein, creatinine and cystatin C. To conclude, protein hydrolysates from herring and salmon rest raw material contained several peptide sequences with known ACE inhibiting activities, and resulted in lower urine concentrations of proteins, cystatin C and glucose when fed to obese Zucker rats.

Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats.

The world's fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.

A low dietary intake of cod protein is sufficient to increase growth, improve serum and tissue fatty acid compositions, and lower serum postprandial glucose and fasting non-esterified fatty acid concentrations in obese Zucker fa/fa rats.

PURPOSE: Studies in rats suggest that fish proteins may improve lipid and glucose regulation and could thus be a potential tool in the treatment of obesity-related comorbidities. To date, all published rat studies on dietary fish protein have been designed with 50 or 100% of dietary proteins from fish. As it is not common, nor advised, to consume fish as the only protein source in a healthy diet, mechanistic studies on the effects of diets with low dose fish proteins are needed. Here, we investigate whether a low dose of cod protein would affect glucose homeostasis and lipid metabolism in obese Zucker fa/fa rats. METHODS: Twelve male obese Zucker fa/fa rats consumed diets where cod proteins accounted for 25% of the total protein intake with the remaining 75% from casein (COD) or 100% of protein as casein (CAS) for 4 weeks. RESULTS: Rats fed COD achieved a higher body weight without affecting adiposity and thigh muscle mass after 4 weeks, but liver weight and hepatic cholesterol level were higher than in CAS-fed rats. Fasting serum level of non-esterified fatty acids and 2 h postprandial glucose level were lower in COD than in CAS. The fatty acid metabolism was beneficially affected by the COD diet, with e.g., higher ratio of n-3/n-6 PUFAs in serum, liver and adipose tissue when compared to CAS. CONCLUSIONS: A low intake of cod protein (25% of protein intake) was sufficient to beneficially affect lipid metabolism and postprandial glucose regulation in obese fa/fa rats.