Obesity has become a global health issue. According to statistics, 2.5 billion adults were classified as overweight in 2022, with over 890 million suffering from obesity. Since 1990, the global adult obesity rate has more than doubled, and the adolescent obesity rate has tripled.[1] Obesity can lead to a range of severe complications, including cardiovascular diseases (CVD), gastrointestinal disorders, type 2 diabetes (T2D), and respiratory diseases. Developing animal models that can simulate the pathological characteristics of human obesity and metabolic syndromes is a key tool for obesity research.
The inbred strain C57BL/6 mice are widely used to establish diet-induced obesity (DIO) mouse models by feeding them a high-fat diet. Studies have shown that compared to C57BL/6N mice, C57BL/6J mice carry a deletion of exons 7-11 of the Nnt gene. The loss of function of this gene can result in mitochondrial metabolic dysfunction in pancreatic β-cells and impaired insulin secretion. In fact, C57BL/6J mice exhibit glucose intolerance and reduced insulin secretion,[2-4] making them less ideal for studying metabolic diseases.
The Role of Nnt Gene Deficiency in Drug Research and the Development of the DIO-B6-M Mouse Model
The Nnt gene is predicted to be involved in NAD binding activity, NAD(P)+ transhydrogenase activity, and NADP binding activity, suggesting that its deficiency may affect drug research involving NADPH-related mechanisms. Therefore, Cyagen has developed the DIO-B6-M mice (Product Code: C001549) on the C57BL/6NCya background, induced by a 60% high-fat diet. This model is suitable for studying obesity, diabetes, inflammation, fatty liver, and other metabolic diseases, as well as for the screening and preclinical efficacy evaluation of related therapeutic drugs.
At 4 weeks of age, male C57BL/6NCya mice began a 60% high-fat diet after a one-week acclimatization period of adaptive feeding. Body weight was monitored regularly, and random blood glucose levels were measured after 25 weeks of high-fat feeding. Results showed that mice in the high-fat diet (HFD) group had significantly higher body weight and random blood glucose levels compared to the normal diet (ND) group.
Figure 1: Body Weight Monitoring and Blood Glucose Test Results of DIO-B6-M Mice
After 25 weeks of high-fat feeding, there was a marked increase in the number of NK cells and macrophages in the peripheral blood of DIO-B6-M mice, indicating an elevated inflammatory response.
Figure 2: Flow Cytometry Analysis of Immune Cells (T Cells, B Cells, NK Cells, and Macrophages) in the Peripheral Blood of Mice After 25 Weeks of HFD Induction
At the 25-week mark, DIO-B6-M mice had significantly elevated levels of total cholesterol (T-CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), as well as aspartate transaminase (AST) and alanine transaminase (ALT), compared to the ND group.
Figure 3: Blood Lipid and Liver Function Indicators in Mice After 25 Weeks of Diet Induction
(TG: Triglycerides; T-CHO: Total Cholesterol; HDL-C: High-Density Lipoprotein Cholesterol; LDL-C: Low-Density Lipoprotein Cholesterol; AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase)
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a drug used to treat diabetes by mimicking the naturally occurring GLP-1 hormone to promote insulin secretion, inhibit glucagon release, and slow gastric emptying, thereby reducing appetite. In addition to its use in diabetes treatment, it is also being studied for its weight-loss effects, especially in obese patients. Its effectiveness in promoting weight loss has made it a highly regarded drug.
Semaglutide Reduces Obesity in DIO Mice
In this study, DIO-B6-M mice were fed a 60% high-fat diet for 12 weeks and then received subcutaneous injections of Semaglutide twice a week. The blank group (B6N+ND) and the control group (B6N+HFD) were injected with the same dose of a control solvent. The results showed that Semaglutide treatment significantly reduced body weight, blood glucose levels, and food intake, while improving glucose tolerance in the DIO-B6-M mice.
Figure 4: DIO-B6-M Mice Can Be Used for Screening of Related Therapeutic Drugs and Preclinical Efficacy Evaluation
The DIO-B6-M mouse model (product code: C001549) is a valuable tool for the research of obesity, diabetes, and other metabolic diseases and related drug development.
DIO-B6-M mice (Product Code: C001549) are developed on the C57BL/6NCya background —avoiding metabolic Nnt gene mutation effects seen in C57BL/6J strain backgrounds — and induced through a 60% high-fat diet starting from 4 weeks of age. These DIO mouse models exhibit phenotypes such as increased body weight, elevated random blood glucose levels, an increase in NK cells and macrophages, as well as elevated blood lipid and liver function indicators. They can be used for research on metabolic diseases such as obesity and diabetes.
Explore Cyagen’s Range of Metabolic and Cardiovascular Disease Models
In addition to the DIO-B6-M model, Cyagen offers a wide range of metabolic disease models and humanized models to meet researchers' needs in metabolic-related studies. Contact us today to learn how our models can support your research into obesity, diabetes, cardiovascular disease, and related metabolic diseases.
Recommended Gene Edited Models for Metabolic and Cardiovascular Disease Research
| Product Number | Product Name | Strain Background | Application |
|---|---|---|---|
| C001507 | B6J-Apoe KO | C57BL/6JCya | Atherosclerosis, Hypercholesterolemia, Metabolic Dysfunction-Associated Steatohepatitis (MASH) |
| C001067 | APOE | C57BL/6NCya | Atherosclerosis |
| C001291 | B6-db/db | C57BL/6JCya | High Blood Sugar and Obesity |
| C001392 | Ldlr KO (em) | C57BL/6JCya | Familial Hypercholesterolemia |
| C001368 | B6-ob/ob (Lep KO) | C57BL/6JCya | Type 2 Diabetes and Obesity |
| C001232 | Uox KO | C57BL/6JCya | Hyperuricemia |
| C001393 | Uox-KO (Prolonged) | C57BL/6JCya | Hyperuricemia |
| C001267 | Atp7b KO | C57BL/6NCya | Copper Metabolism Disorder, Wilson's Disease |
| C001265 | Foxj1 KO | C57BL/6NCya | Primary Ciliary Dyskinesia |
| C001266 | Usp26 KO | C57BL/6NCya | Klinefelter Syndrome |
| C001273 | Fah KO | C57BL/6NCya | Phenylketonuria Type 1 |
| C001383 | Alb-Cre/LSL-hLPA | C57BL/6NCya | Cardiovascular Targets |
| C001421 | B6-hGLP-1R | C57BL/6NCya | Metabolic Targets |
| C001400 | B6J-hANGPTL3 | C57BL/6JCya | Metabolic Targets |
| C001493 | FVB-Abcb1a&Abcb1b DKO (Mdr1a/b KO) | FVB | Diseases Related to Blood-Brain Barrier Permeability |
| C001532 | Serping1 KO | C57BL/6JCya | Hereditary Angioedema(HAE) |
Other Models for Metabolic and Cardiovascular Disease Research: Spontaneous, Induced, Composite, & Surgical Models
| Diet-Induced Obesity (DIO) Model | Type 2 Diabetes Mellitus (T2DM) Models | Type 1 Diabetes Mellitus (T1DM) Models | Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Model |
| Chemically Induced MASLD Model | MASLD Model | Composite MASLD Model | Composite Arteriosclerosis Model |
| Arteriosclerosis Model | Acute Pancreatitis Model | Chronic Pancreatitis Model | DIO&CCL4 Induced MASH(NASH) Mouse Model |
References:
[1] World Health Organization (WHO). (2024, March 1). Obesity and overweight. Retrieved from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
[2] Simon MM, Greenaway S, White JK, Fuchs H, Gailus-Durner V, Wells S, Sorg T, Wong K, Bedu E, Cartwright EJ, Dacquin R, Djebali S, Estabel J, Graw J, Ingham NJ, Jackson IJ, Lengeling A, Mandillo S, Marvel J, Meziane H, Preitner F, Puk O, Roux M, Adams DJ, Atkins S, Ayadi A, Becker L, Blake A, Brooker D, Cater H, Champy MF, Combe R, Danecek P, di Fenza A, Gates H, Gerdin AK, Golini E, Hancock JM, Hans W, Hölter SM, Hough T, Jurdic P, Keane TM, Morgan H, Müller W, Neff F, Nicholson G, Pasche B, Roberson LA, Rozman J, Sanderson M, Santos L, Selloum M, Shannon C, Southwell A, Tocchini-Valentini GP, Vancollie VE, Westerberg H, Wurst W, Zi M, Yalcin B, Ramirez-Solis R, Steel KP, Mallon AM, de Angelis MH, Herault Y, Brown SD. A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains. Genome Biol. 2013 Jul 31;14(7):R82.
[3] Freeman H, Shimomura K, Horner E, Cox RD, Ashcroft FM. Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion. Cell Metab. 2006 Jan;3(1):35-45.
[4] Hull RL, Willard JR, Struck MD, Barrow BM, Brar GS, Andrikopoulos S, Zraika S. High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains. J Endocrinol. 2017 Apr;233(1):53-64.
