The Impact of Different Animal-Derived Protein Sources on Adiposity and Glucose Homeostasis during Ad Libitum Feeding and Energy Restriction in Already Obese Mice.

Low-fat diets and energy restriction are recommended to prevent obesity and to induce weight loss, but high-protein diets are popular alternatives. However, the importance of the protein source in obesity prevention and weight loss is unclear. The aim of this study was to investigate the ability of different animal protein sources to prevent or reverse obesity by using lean or obese C57BL/6J mice fed high-fat/high-protein or low-fat diets with casein, cod or pork as protein sources. Only the high-fat/high-protein casein-based diet completely prevented obesity development when fed to lean mice. In obese mice, ad libitum intake of a casein-based high-fat/high-protein diet modestly reduced body mass, whereas a pork-based high-fat/high-protein diet aggravated the obese state and reduced lean body mass. Caloric restriction of obese mice fed high-fat/high-protein diets reduced body weight and fat mass and improved glucose tolerance and insulin sensitivity, irrespective of the protein source. Finally, in obese mice, ad libitum intake of a low-fat diet stabilized body weight, reduced fat mass and increased lean body mass, with the highest loss of fat mass found in mice fed the casein-based diet. Combined with caloric restriction, the casein-based low-fat diet resulted in the highest loss of fat mass. Overall, the dietary protein source has greater impact in obesity prevention than obesity reversal.

Effects of Frozen Storage on Phospholipid Content in Atlantic Cod Fillets and the Influence on Diet-Induced Obesity in Mice.

A large fraction of the n-3 polyunsaturated fatty acids (PUFAs) in cod fillet is present in the form of phospholipids (PLs). Freezing initiates hydrolysis of the PLs present in the fillet. Here, we compared the effects of Western diets based on frozen cod, fresh cod or pork with a diet based on casein in male C57BL/6J mice fed for 12 weeks at thermoneutrality. Diets based on fresh cod contained more PL-bound n-3 PUFAs (3.12 mg/g diet) than diets based on frozen cod (1.9 mg/g diet). Mice fed diets containing pork and fresh cod, but not frozen cod, gained more body and fat mass than casein-fed mice. Additionally, the bioavailability of n-3 PUFAs present in the cod fillets was not influenced by storage conditions. In a second experiment, diets with pork as the protein source were supplemented with n-3 PUFAs in the form of PL or triacylglycerol (TAG) to match the levels of the diet containing fresh cod. Adding PL-bound, but not TAG-bound, n-3 PUFAs, to the pork-based diet increased body and fat mass gain. Thus, supplementation with PL-bound n-3 PUFAs did not protect against, but rather promoted, obesity development in mice fed a pork-based diet.

The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice.

The notion that the obesogenic potential of high fat diets in rodents is attenuated when the protein:carbohydrate ratio is increased is largely based on studies using casein or whey as the protein source. We fed C57BL/6J mice high fat-high protein diets using casein, soy, cod, beef, chicken or pork as protein sources. Casein stood out as the most efficient in preventing weight gain and accretion of adipose mass. By contrast, mice fed diets based on pork or chicken, and to a lesser extent mice fed cod or beef protein, had increased adipose tissue mass gain relative to casein fed mice. Decreasing the protein:carbohydrate ratio in diets with casein or pork as protein sources led to accentuated fat mass accumulation. Pork fed mice were more obese than casein fed mice, and relative to casein, the pork-based feed induced substantial accumulation of fat in classic interscapular brown adipose tissue accompanied by decreased UCP1 expression. Furthermore, intake of a low fat diet with casein, but not pork, as a protein source reversed diet-induced obesity. Compared to pork, casein seems unique in maintaining the classical brown morphology in interscapular brown adipose tissue with high UCP1 expression. This was accompanied by increased expression of genes involved in a futile cycling of fatty acids. Our results demonstrate that intake of high protein diets based on other protein sources may not have similar effects, and hence, the obesity protective effect of high protein diets is clearly modulated by protein source.

Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.

High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD.

Intake of a Western diet containing cod instead of pork alters fatty acid composition in tissue phospholipids and attenuates obesity and hepatic lipid accumulation in mice.

The content of the marine n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is far lower in lean than in fatty seafood. Cod filets contain less than 2g fat per kg, whereof approximately 50% is EPA and DHA. However, a large fraction of these n-3 PUFAs is present in the phospholipid (PL) fraction and may have high bioavailability and capacity to change the endocannabinoid profile. Here we investigated whether exchanging meat from a lean terrestrial animal with cod in a background Western diet would alter the endocannabinoid tone in mice and thereby attenuate obesity development and hepatic lipid accumulation. Accordingly, we prepared iso-caloric diets with 15.1 energy (e) % protein, 39.1 e% fat and 45.8 e% carbohydrates using freeze-dried meat from cod filets or pork sirloins, and using a combination of soybean oil, corn oil, margarine, milk fat, and lard as the fat source. Compared with mice receiving diets containing pork, mice fed cod gained less adipose tissue mass and had a lower content of hepatic lipids. This was accompanied by a lower n-6 to n-3 ratio in liver PLs and in red blood cells (RBCs) in the mice. Furthermore, mice receiving the cod-containing diet had lower circulating levels of the two major endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoylglycerol. Together, our data demonstrate that despite the relatively low content of n-3 PUFAs in cod fillets, the cod-containing diet could exert beneficial metabolic effects.