The common use of improper control diets in diet-induced metabolic disease research confounds data interpretation: the fiber factor

Abstract

Diets used to induce metabolic disease are generally high in fat and refined carbohydrates and importantly, are usually made with refined, purified ingredients. However, researchers will often use a low fat grain-based (GB) diet containing unrefined ingredients as the control diet. Such a comparison between two completely different diet types makes it impossible to draw conclusions regarding the phenotypic differences driven by diet. While many compositional differences can account for this, one major difference that could have the greatest impact between GB and purified diets is the fiber content, both in terms of the level and composition. We will review recent data showing how fiber differences between GB diets and purified diets can significantly influence gut health and microbiota, which itself can affect metabolic disease development. Researchers need to consider the control diet carefully in order to make the best use of precious experimental resources.

The LepRdb/db mice model for studying glycation in the context of diabetes

“…More broadly, the overall composition of the so‐called control diets in animal studies is an important consideration with regard to their relevance when animals fed control diets are compared with animals fed specific diets. For instance, a recent study has shown that the fibre content may not be equal in control diets containing unrefined ingredients and in custom‐made “high fat” diets . This difference in fibre content, just like the difference of AGE content that we report here, may affect the metabolic disorders followed in animal studies.…”

Effects of Rodent Diet Choice and Fiber Type on Data Interpretation of Gut Microbiome and Metabolic Disease Research

“…As described in detail above, purified ingredient diets are very different from GB diets, and as one may expect, these differences can play a role in data interpretation when both are used in the same study. The problem with using a GB diet as a control diet for a high fat purified ingredient diet has been discussed and recent surveys suggest this problem still can be found in many studies (Fodde, Schmitt, Schewe, & Augenlicht, ; Pellizzon & Ricci, ; Rendina‐Ruedy & Smith, ; Warden & Fisler, ). In a recent survey of 69 publications including Cell , Nature , and Diabetes using search terms ‘mouse high fat’, it was found that only 18.8% of studies used a matched purified ingredient low fat control diet for the high fat diet while 40.6% used a GB diet as the low fat ‘control’ diet, with the remaining 40.6% of papers not providing sufficient data to determine what control diet was used (Pellizzon & Ricci, ).…”

“…The problem with using a GB diet as a control diet for a high fat purified ingredient diet has been discussed and recent surveys suggest this problem still can be found in many studies (Fodde, Schmitt, Schewe, & Augenlicht, 2017;Pellizzon & Ricci, 2018;Rendina-Ruedy & Smith, 2016;Warden & Fisler, 2008). In a recent survey of 69 publications including Cell, Nature, and Diabetes using search terms 'mouse high fat', it was found that only 18.8% of studies used a matched purified ingredient low fat control diet for the high fat diet while 40.6% used a GB diet as the low fat 'control' diet, with the remaining 40.6% of papers not providing sufficient data to determine what control diet was used (Pellizzon & Ricci, 2018). A study by Chassaing et al (Chassaing et al, 2015) brought this issue to light when they used 3 different diets in their study: a GB diet (Purina 5001) and 2 purified ingredient diets, one with 10 kcal% fat and the other with 60 kcal% fat, both with cellulose as the only source of fiber.…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…363,367 Poor reporting of research-relevant diet factors such as differences between purified and natural ingredient diets have attracted attention and concern recently. 10, 358,368 Research diets are frequently provided ad libitum to rodents on shorter term studies. Diet restriction in long-term studies usually improves survival and reduces neoplastic, kidney, inflammatory, and other lesions.…”