Relevance of control diet choice in metabolic studies: impact in glucose homeostasis and vascular function

Abstract

The experimental approach for the study of cardiometabolic disorders requires the use of animal models fed with commercial diets whose composition differs notably, even between diets used for control groups. While chow diets are usually made of agricultural by-products, purified low-fat diets (LF) contain a higher percentage of easy metabolizable carbohydrates, together with a reduced amount of polyunsaturated fatty acids, micronutrients and fiber, all associated with metabolic and vascular dysfunction. We hypothesize that the LF diet, commonly used in control animals, could promote adverse vascular and metabolic outcomes. To address this issue, 5-week-old male C57BL6J mice were fed with a standard (Chow) or a LF diet for 6 weeks. Changes in body weight, adiposity, biochemical parameters, systemic and aortic insulin sensitivity and endothelial function were recorded. LF diet did not modify body weight but significantly impaired systemic glucose tolerance and increased triglycerides and cholesterol levels. Endothelial function and aortic insulin sensitivity were significantly impaired in the LF group, due to a reduction of NO availability. These findings highlight the importance of selecting the proper control diet in metabolic studies. It may also suggest that some cardiometabolic alterations obtained in experimental studies using LF as a control diet may be underestimated.

Diet-Induced Models of Non-Alcoholic Fatty Liver Disease: Food for Thought on Sugar, Fat, and Cholesterol

“…It is already established that dietary cholesterol has an important role in the progression of NAFLD to NASH by inducing inflammation and fibrosis [ 47 , 48 ]. Only a small increase in cholesterol (0.06%) is needed to detect an increase in plasma cholesterol in mice [ 49 ], demonstrating its potent effect, even in small doses. However, much more seems to be needed to see pathogenic effects in mouse liver tissue.…”

“…Gonzalez-Blázquez et al recently compared a standard animal facility chow diet (24% kcal protein, 58% kcal carbohydrate, 18% kcal fat) to a low-fat control diet (18% kcal protein, 71.8% kcal carbohydrate, 10.2% kcal fat) matched in macronutrient source to the supplier’s high-fat diet [ 49 ]. In addition to being higher in total carbohydrates, the matched control diet is largely composed of refined sugars (sucrose, dextrin, and maltodextrin) compared to the crushed grain, wheat and legume used in the standard animal facility chow diet [ 49 ]. The matched control diet also contains lower levels of PUFAs and slightly higher cholesterol content (under 0.1%) [ 49 ].…”

“…In addition to being higher in total carbohydrates, the matched control diet is largely composed of refined sugars (sucrose, dextrin, and maltodextrin) compared to the crushed grain, wheat and legume used in the standard animal facility chow diet [ 49 ]. The matched control diet also contains lower levels of PUFAs and slightly higher cholesterol content (under 0.1%) [ 49 ]. Interestingly, mice fed the matched diet have higher energy intake, plasma insulin, glucose, cholesterol, and triglycerides compared to the chow-fed mice after 6 weeks [ 49 ].…”

Cardiometabolic Syndrome: An Update on Available Mouse Models

“…Furthermore, for diet-induced CMS the selection of proper control diet is crucial as cardiometabolic alterations were found to be underestimated in low fat diet-treated controls. 139 Another emerging issue that needs to be addressed is the impact of sex in the study of CMS. Traditionally, male mice are preferred over females because of the known development of a more severe disease phenotype and because of the concern that the estrous cycle induces variability in traits that complicate experimental designs; however, the latter has been debated.…”

Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice

“…In fact, whereas the main source of fat in chow diets is vegetable and fish oil, purified HF diets mainly contain lard, especially rich in saturated fatty acids (SFA) but very limited in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). In addition, purified diets also provide a greater amount of easily metabolizable carbohydrates as compared to standard chow diets for rodents [9,10]. Therefore, commercial HF diets might not be fully representative of common diets ingested by the general population worldwide.…”