Herring Milt and Herring Milt Protein Hydrolysate Reduce Weight Gain and Improve Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese Mice

Abstract Objectives The present study was designed to examine the effect of herring milt dry powder (HMDP) on glucose homeostasis and related metabolic phenotypes and compare its efficacy with herring milt protein hydrolysate (HMPH) in diet-induced obese and insulin resistant mice. Methods Male C57BL/6 J mice were pretreated with a high-fat diet for 7 weeks were divided into 3 groups where one group continued on the high-fat diet and used as the obese and insulin resistant control (HFC) and the other two groups were fed a modified HFC diet where 70% of casein was replaced with an equal percentage of protein derived from HMDP or HMPH. A group of mice fed a low-fat diet all the time was used as the normal or low-fat control (LFC). Body weight was obtained weekly and food intake was recorded daily. Semi-fating (4–6 hr) blood glucose was measured every other week using a glucometer using the blood from tail vein. Oral glucose tolerance was measured twice during weeks 5 and 9, respectively, and insulin tolerance was determined during week 7 of the treatment. At the end of the experiment, serum was obtained following overnight fasting for the measurement of fasting insulin, leptin, free fatty acids and lipids as well as other glucose metabolism-related biomarkers. Results During the 9-week treatment period, mice on the high-fat diet maintained significantly higher body weight and semi-fasting blood glucose levels and exhibited impaired oral glucose tolerance and insulin resistance relative to mice on the low-fat diet. At the end of the study, the analysis of fasting blood samples revealed that mice on the high-fat diet had increases in serum insulin, leptin, free fatty acids and cholesterol levels. Mice fed the high-fat diet also showed an increase in insulin resistance index and a decrease in β-cell function index. Compared to mice on the high-fat diet, the 70% replacement of dietary casein with an equal percentage of protein derived from HMDP or HMPH reversed or markedly improved these parameters, and HMDP and HMPH showed similar effects. Conclusions The results demonstrate that replacing dietary casein with the same amount of protein derived from either HMDP or HMPH prevents and improves high-fat-diet-induced obesity and insulin resistance. Funding Sources Atlantic Canada Opportunity Agency through the Atlantic Innovation Fund grant (no. 193,594) and National Research Council of Canada – NHP program.

Download Full-text

Herring Milt and Herring Milt Protein Hydrolysate Are Equally Effective in Improving Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese- and Insulin-Resistant Mice

Marine Drugs ◽

10.3390/md18120635 ◽

2020 ◽

Vol 18 (12) ◽

pp. 635

Author(s):

Yanwen Wang ◽

Sandhya Nair ◽

Jacques Gagnon

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Cell Function ◽

Protein Hydrolysate ◽

High Fat ◽

Β Cell ◽

Insulin Resistant ◽

Β Cell Function ◽

Casein Protein ◽

Dietary Casein

Although genetic predisposition influences the onset and progression of insulin resistance and diabetes, dietary nutrients are critical. In general, protein is beneficial relative to carbohydrate and fat but dependent on protein source. Our recent study demonstrated that 70% replacement of dietary casein protein with the equivalent quantity of protein derived from herring milt protein hydrolysate (HMPH; herring milt with proteins being enzymatically hydrolyzed) significantly improved insulin resistance and glucose homeostasis in high-fat diet-induced obese mice. As production of protein hydrolysate increases the cost of the product, it is important to determine whether a simply dried and ground herring milt product possesses similar benefits. Therefore, the current study was conducted to investigate the effect of herring milt dry powder (HMDP) on glucose control and the associated metabolic phenotypes and further to compare its efficacy with HMPH. Male C57BL/6J mice on a high-fat diet for 7 weeks were randomized based on body weight and blood glucose into three groups. One group continued on the high-fat diet and was used as the insulin-resistant/diabetic control and the other two groups were given the high-fat diet modified to have 70% of casein protein being replaced with the same amount of protein from HMDP or HMPH. A group of mice on a low-fat diet all the time was used as the normal control. The results demonstrated that mice on the high-fat diet increased weight gain and showed higher blood concentrations of glucose, insulin, and leptin, as well as impaired glucose tolerance and pancreatic β-cell function relative to those on the normal control diet. In comparison with the high-fat diet, the replacement of 70% dietary casein protein with the same amount of HMDP or HMPH protein decreased weight gain and significantly improved the aforementioned biomarkers, insulin sensitivity or resistance, and β-cell function. The HMDP and HMPH showed similar effects on every parameter except blood lipids where HMDP decreased total cholesterol and non-HDL-cholesterol levels while the effect of HMPH was not significant. The results demonstrate that substituting 70% of dietary casein protein with the equivalent amount of HMDP or HMPH protein protects against obesity and diabetes, and HMDP is also beneficial to cholesterol homeostasis.

Download Full-text

The role of dietary fat in obesity-induced insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00323.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. E989-E997 ◽

Cited By ~ 7

Author(s):

Denise E. Lackey ◽

Raul G. Lazaro ◽

Pingping Li ◽

Andrew Johnson ◽

Angelina Hernandez-Carretero ◽

...

Keyword(s):

Insulin Resistance ◽

Dietary Fat ◽

High Fat Diet ◽

Caloric Intake ◽

High Fat ◽

Low Fat ◽

Feeding Method ◽

Low Fat Diet ◽

Obesity And Diabetes

Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease.

Download Full-text

Herring Milt Protein Hydrolysate Improves Insulin Resistance in High-Fat-Diet-Induced Obese Male C57BL/6J Mice

Marine Drugs ◽

10.3390/md17080456 ◽

2019 ◽

Vol 17 (8) ◽

pp. 456 ◽

Cited By ~ 3

Author(s):

Yanwen Wang ◽

Jacques Gagnon ◽

Sandhya Nair ◽

Shelly Sha

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

High Fat Diet ◽

Protein Hydrolysate ◽

Fasting Blood Glucose ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

High Fat ◽

Diet Induced Obesity ◽

Dietary Casein

Protein consumption influences glucose homeostasis, but the effect depends on the type and origin of proteins ingested. The present study was designed to determine the effect of herring milt protein hydrolysate (HPH) on insulin function and glucose metabolism in a mouse model of diet-induced obesity. Male C57BL/6J mice were pretreated with a low-fat diet or a high-fat diet for 6 weeks. Mice on the high-fat diet were divided into four groups where one group continued on the high-fat diet and the other three groups were fed a modified high-fat diet where 15%, 35%, and 70%, respectively, of casein was replaced with an equal percentage of protein derived from HPH. After 10 weeks, mice that continued on the high-fat diet showed significant increases in body weight, blood glucose, insulin, and leptin levels and exhibited impaired oral glucose tolerance, insulin resistance, and pancreatic β-cell dysfunction. Compared to mice fed the high-fat diet, the 70% replacement of dietary casein with HPH protein reduced body weight, semi-fasting blood glucose, fasting blood glucose, insulin, leptin, and cholesterol levels and improved glucose tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) indices. The 35% replacement of dietary casein with HPH protein showed moderate effects, while the 15% replacement of dietary casein with HPH protein had no effects. This is the first study demonstrating that replacing dietary casein with the same amount of protein derived from HPH can prevent high-fat-diet-induced obesity and insulin resistance.

Download Full-text

A low-fat diet has a higher potential than energy restriction to improve high-fat diet-induced insulin resistance in mice

Metabolism ◽

10.1053/meta.2002.32725 ◽

2002 ◽

Vol 51 (6) ◽

pp. 695-701 ◽

Cited By ~ 33

Author(s):

Martin Muurling ◽

Miek C. Jong ◽

Ronald P. Mensink ◽

Gerard Hornstra ◽

Vivian E.H. Dahlmans ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Energy Restriction ◽

High Fat ◽

Low Fat ◽

Low Fat Diet

Download Full-text

Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0644 ◽

2017 ◽

Vol 42 (8) ◽

pp. 841-849 ◽

Cited By ~ 8

Author(s):

Sandhya Nair ◽

Jacques Gagnon ◽

Claude Pelletier ◽

Nadia Tchoukanova ◽

Junzeng Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Glucose Tolerance ◽

Chronic Inflammation ◽

High Fat Diet ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Obese Rats ◽

Shrimp Oil

Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.

Download Full-text

Influence of a high-fat diet during chronic hyperglycemia on beta-cell function in pancreatic islet transplants to streptozotocin-diabetic rats

Acta Endocrinologica ◽

10.1530/eje.0.1440521 ◽

2001 ◽

pp. 521-527 ◽

Cited By ~ 2

Author(s):

S Hiramatsu ◽

V Grill

Keyword(s):

Fatty Acids ◽

Beta Cell ◽

High Fat Diet ◽

Beta Cell Function ◽

Cell Function ◽

High Fat ◽

Negative Effects ◽

Low Fat ◽

Low Fat Diet ◽

Chronic Hyperglycemia

Chronically elevated non-esterified fatty acids (NEFAs) can exert negative effects on beta-cell function both in vitro and in vivo. Negative effects of fatty acids have been difficult to evaluate in overt diabetes because of the attendant hyperglycemia that gives rise to the confounding influence of 'glucotoxicity'. In this work, we tested for the effects of NEFAs in diabetes by (i) taking into account potential effects of prevailing levels of hyperglycemia, and (ii) focusing on lingering (and therefore possibly more serious) effects. A diabetic transplantation model was used in which two islet grafts with 200 and 20 rat islets respectively were transplanted under the kidney capsule of syngeneic recipients previously made diabetic by streptozotocin injection. Rats were then fed either a high-fat or a low-fat diet for 7 weeks, followed by 1 week of normal laboratory chow. During dietary intervention, food was consumed ad libitum in one protocol, but was restricted in the low-fat group in a second protocol (in order to match blood-glucose levels). A high-fat diet did not affect body weight. At the end of the protocols, graft-bearing kidneys were isolated and perfused. Insulin responses to 27.8 mM glucose in perfusion were uniformly absent, in keeping with previously documented effects of chronic hyperglycemia. In contrast, 10 mM arginine induced a marked increase in insulin secretion after a low-fat diet, an effect that was significantly reduced after a high-fat diet (109 +/- 39 vs 13 +/- 15 fmol/min (P < 0.05) and 95 +/- 18 vs 32 +/- 5 fmol/min (P < 0.05) in the 2 protocols respectively). Regardless of protocol, no effect of diet could be detected on graft contents of insulin or preproinsulin mRNA. Thus, under conditions in which influences of chronic hyperglycemia could be accounted for, a previous high-fat diet with elevated NEFAs inhibited arginine-induced insulin secretion; however, the results indicate that insulin biosynthesis and/or beta-cell mass were not affected.

Download Full-text

Abstract 480: Exacerbation of Arterial Stiffness in Obese Adiponectin Deficient Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.480 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Megha Murali ◽

Carla Taylor ◽

Peter Zahradka ◽

Jeffrey Wigle

Keyword(s):

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

High Fat Diet ◽

Pulse Wave ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

High Fat Diets ◽

Fat Diets

Background and Objective: Arterial stiffness is recognized as being an independent predictor of incipient vascular disease associated with obesity and metabolic syndrome. In obese subjects, the decrease in the plasma level of adiponectin, an anti-diabetic and anti-atherogenic adipokine, is well known. Hence the aim of our study was to examine the effect of loss of adiponectin on the development of arterial stiffness in response to a high fat diet. Methods and Results: Male 8-week old adiponectin knockout (APN KO) and C57BL/6 (control) mice were fed a high fat diet (60% Calories from fat) for 12 weeks to induce obesity and insulin resistance (n=10/group). APN KO and C57BL/6 mice were fed a low fat diet (10% Calories from fat) and used as lean controls (n=10/group). After 12 weeks on the high fat diet, the APN KO mice weighed significantly more than the C57BL/6 mice (45.1±1.3 g vs 40.1±1.1 g, p=0.0008) but there was no difference in the final weights between genotypes fed the low fat diet. APN KO mice on both high and low fat diets for 12 weeks developed insulin resistance as measured by oral glucose tolerance test (Area under curve (AUC) mmol/L х min = 437±70 and 438±57) as compared to the C57BL/6 mice fed low or high fat diets (AUC mmol/L х min = 251±27 and 245±43). Arterial stiffness was determined by Doppler pulse wave velocity analysis of the femoral artery. Pulse wave velocity was increased in APN KO mice fed a high fat diet relative to those fed the low fat diet (12.56±0.78 cm/s vs 9.47±0.95 cm/s, p=0.0035; n=8-10). Pulse wave velocity was not different between C57BL/6 control mice on the low or high fat diets (10.63±0.73 cm/s and 10.86±0.50 cm/s), thus revealing that only mice deficient in adiponectin developed arterial stiffness in response to high fat diet. Conclusions: Potentiation of the vascular stiffness in diet-induced obese APN KO mice indicates that adiponectin has a role in modulating vascular structure and the APN KO mouse models the vascular changes that occur in human obesity and metabolic disorders. Morphometric analysis of the aortic tissues for vessel thickness and expression of extracellular proteins will further validate the potential role of adiponectin on the maintenance of arterial elasticity in addition to its known effect on eNOS mediated vasoprotection.

Download Full-text

Influence of gender on OVA-induced airway inflammation in C57/B6J mice on a high-fat diet

European Journal of Inflammation ◽

10.1177/2058739218760946 ◽

2018 ◽

Vol 16 ◽

pp. 205873921876094 ◽

Cited By ~ 1

Author(s):

Gang Yu ◽

Lili Zhu ◽

Haiyan Li ◽

Youyou Shao ◽

Lei Chong ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Inflammatory Cells ◽

Normal Weight ◽

Male Mice ◽

High Fat ◽

Low Fat ◽

Control Male ◽

Low Fat Diet ◽

Asthma Group

Overweight/obesity has been suggested as a risk factor for asthma development, and prospective studies have confirmed that high body weight precedes asthma symptoms. However, the nature of the association between overweight/obese status and asthma remains unclear. Animal models of obesity-related asthma are very useful for understanding disease pathophysiology. Although C57/B6J mice are the most widely used animal model for researching obesity-related asthma, gender differences are not always taken into consideration. Therefore, to explore the effect of gender on the development of obesity-related asthma, both female and male C57/B6J mice were used in this study. The mice were fed with a high-fat diet or a low-fat diet as control. Body weight, body length, liver weight, and Lee’s Index were used to evaluate obesity status, and lung histology, lung inflammatory cells infiltration, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined for asthma evaluation. We found that the mean body weight of male mice on a high-fat diet gradually increased and was significantly higher than control male mice on a low-fat diet ( P < 0.01), while no significant differences were found between female mice at the end of 12 weeks of feeding. Furthermore, the obese asthma group female and male mice exhibited significantly high inflammatory cells infiltration than normal weight or obese female and male mice ( P < 0.01). However, the obese asthma group presented higher Neu infiltration, Th1 cytokine, and interferon gamma (IFNγ) concentrations in BALF than the asthma group in both the genders ( P < 0.01). In conclusion, both female and male mice are suitable for the obesity-related asthma model, although male mice might be more stable. Besides, obesity-related asthma is not Th2 type asthma.

Download Full-text

SERUM LIPID PROFILE;

The Professional Medical Journal ◽

10.29309/tpmj/2008.15.04.2863 ◽

2008 ◽

Vol 15 (04) ◽

pp. 500-507

Author(s):

MUHAMMAD ANWAR BURIRO ◽

MUHAMMAD TAYYAB

Keyword(s):

Sunflower Oil ◽

High Fat Diet ◽

Serum Lipid ◽

Nigella Sativa ◽

Albino Rats ◽

High Fat ◽

Low Fat ◽

Control Groups ◽

Low Fat Diet ◽

Lipid Fractions

Objective: To determine the effects of Nigella sativa and sunflower oil diet intake on serum lipid profile in albino rats. Material& Methods: Eighty four albino rats with equal number of males and females were selected for the study, they were divided into six differentgroups, Control groups1,111,V,were given low fat diet(3%),high fat diet(20%), high fat diet supplemented with bile salt (1% colic acid) andantithyroid drug (0.5% propylthiouracil). The Experimental groups were given the above diets with supplemented Nigella sativa. Low fat dietincreased all the lipid fractions significantly when given at12 and 24 weeks duration as compared to 0 week. Results: The high fat diet whengiven at different intervals decreased all lipid fractions significantly as compared to baseline level. The high fat diet with propylthiouracil andbile salt also increased all the lipid fractions and the increase was more as compared to previous groups. The supplements of Nigella sativain the groups decreased all the lipid fractions significantly as compared to the control groups except HDL-c, which was significantly increasedin all the experimental groups as compared to control groups. Conclusion: On the basis of these findings conclusions are made, that Nigellasativa has got TG,TC, and LDL-c lowering and HDL-c raising effects.3% sunflower oil low fat diet has got TG,TC,HDL-c, and LDL-c raisingeffects.20% sunflower oil high fat diet has got TG,TC,HDL-c and LDL-c lowering effects. Both Nigella sativa and sunflower oil have got lowatherogenic index (TC/HDL) and may be recommended in hyperlipidaemic patients or normal individuals.

Download Full-text

CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00215.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. E973-E983 ◽

Cited By ~ 3

Author(s):

Annie Hasib ◽

Chandani K. Hennayake ◽

Deanna P. Bracy ◽

Aimée R. Bugler-Lamb ◽

Louise Lantier ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

High Fat Diet ◽

Critical Role ◽

Chow Diet ◽

Wild Type ◽

High Fat ◽

Insulin Resistant ◽

Beneficial Effects

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.

Download Full-text