C57BL/6J substrain differences in response to high-fat diet intervention

Abstract

C57BL/6J-related mouse strains are widely used animal models for diet-induced obesity (DIO). Multiple vendors breed C57BL/6J-related substrains which may introduce genetic drift and environmental confounders such as microbiome differences. To address potential vendor/substrain specific effects, we compared DIO of C57BL/6J-related substrains from three different vendors: C57BL/6J (Charles Rivers), C57BL/6JBomTac (Taconic Bioscience) and C57BL/6JRj (Janvier). After local acclimatization, DIO was induced by either a high-fat diet (HFD, 60% energy from fat) or western diet (WD, 42% energy from fat supplemented with fructose in the drinking water). All three groups on HFD gained a similar amount of total body weight, yet the relative amount of fat percentage and mass of inguinal-and epididymal white adipose tissue (iWAT and eWAT) was lower in C57BL/6JBomTac compared to the two other C57BL/6J-releated substrains. In contrast to HFD, the three groups on WD responded differently in terms of body weight gain, where C57BL/6J was particularly prone to WD. This was associated with a relative higher amount of eWAT, iWAT, and liver triglycerides. Although the HFD and WD had significant impact on the microbiota, we did not observe any major differences between the three groups of mice. Together, these data demonstrate significant differences in HFD-and WD-induced adiposity in C57BL/6J-related substrains, which should be considered in the design of animal DIO studies. Experimental studies within fields of DIO and the following metabolic consequences most often involves in vivo mouse models. It is generally known that different commercially available inbred mouse strains do not respond similarly to HFD 1-5. For example, whereas C57BL/6 usually gain weight on HFD, the 129SvEv strain is resistant to DIO 2,6. Some of these differences may be explained by the genetic variance 7-9. In addition, environmental factors such as housing facilities impacting the microbiota has been suggested to affect susceptibility to DIO 2,10,11 (and reviewed in 12). Importantly, multiple substrains of C57BL/6 are commercially available and many of these substrains are thus widely used in the field of obesity and diabetes research 13-15. An extensive whole-genome comparison between the C57BL/6 substrains, C57BL/6J and C57BL/6N, identified several genetic variants, including several single nucleotide polymorphisms (SNPs) 7,8 likely impacting physiology. Moreover, several studies have shown that C57BL/6J are more glucose intolerant than the C57BL/6N due to a functional deletion of exon 7-11 in the gene encoding nicotinamide nucleotide transhydrogenase (Nnt) 16-20. NNT is an integral protein located in the inner mitochondrial membrane and it is a central source of mitochondrial NADPH important

Dietary Options for Rodents in the Study of Obesity

“…Since C57BL/6 mouse strains are widely used in diet-induced obesity (DIO) studies, different substrains of C57BL/6 mice are also available. They include genetic and environmental differences such as those present in the microbiome [27] as well as differences in response to an HFD feeding [27][28][29][30]. A study carried out in C57BL/6JRj and C57BL/6NTac mice substrains, reported important differences in response to an HFD, and concluded that the C57BL/6JRj strain is protected against DIO regardless of physical activity and food intake [29].…”

Immune spleen cells attenuate the inflammatory profile of the mesenteric perivascular adipose tissue in obese mice

“…Moreover, this difference may be explained by the fact that the C57Bl/6 mice used here do not have a mutation in the nicotinamide nucleotide transhydrogenase gene. It has been reported that C57Bl/6 J substrains that present this mutation display a higher susceptibility to gain fat mass and to an impairment of glucose tolerance induced by HFD in comparison to C57Bl/6 without the mutation 36 , 37 .…”

Anti-NAFLD Effect of Djulis Hull and Its Major Compound, Rutin, in Mice with High-Fat Diet (HFD)-Induced Obesity

“…Seven-week-old male C57BL/6J mice from the National Laboratory Animal Center (Taipei, Taiwan) were housed in a temperature-controlled (22 ± 2 °C) animal center with a 12:12 h light–dark cycle (light on at 07:00). C57BL/6J related mouse strains are widely used in diet-induced obesity animal models [ 18 ]. All animal experiments were approved by the Institutional Animal Care and Use Committee of Taipei Medical University (LAC-2020-0229) and performed in accordance with the NIH guide for the care and use of laboratory animals.…”

“…Plasma lipids were extracted using the Folch method as previously described [ 18 ] with slight modifications. Briefly, 1.5 mL of methanol was added to a 40 µL plasma sample, followed by the addition of 3 mL of CHCl 3 and incubation for 1 h at room temperature with vortex mixing.…”