Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

Isabelle E Logan; Gerd Bobe; Cristobal L Miranda; Stephany Vasquez-Perez; Jaewoo Choi; Malcolm B Lowry; Thomas J Sharpton; Andrey Morgun; Claudia S Maier; Jan F Stevens; Natalia Shulzhenko; Adrian F Gombart

doi:10.3390/microorganisms8040520

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

Microorganisms. 2020 Apr 5;8(4):520. doi: 10.3390/microorganisms8040520.

Authors

Affiliations

¹ Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
² Department of Animal Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
³ Department of Pharmaceutical Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
⁴ Carlson College of Veterinary Medicine, Corvallis, OR, 97331, USA.
⁵ Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
⁶ Department of Microbiology, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
⁷ Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA.
⁸ Department of Statistics, Oregon State University, Corvallis, OR 97331, USA.
⁹ Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA.
¹⁰ Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
¹¹ Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.

Abstract

A calorie-dense diet is a well-established risk factor for obesity and metabolic syndrome (MetS), whereas the role of the intestinal microbiota (IMB) in the development of diet-induced obesity (DIO) is not completely understood. To test the hypothesis that Swiss Webster (Tac:SW) mice can develop characteristics of DIO and MetS in the absence of the IMB, we fed conventional (CV) and germ-free (GF) male Tac:SW mice either a low-fat diet (LFD; 10% fat derived calories) or a high-fat diet (HFD; 60% fat derived calories) for 10 weeks. The HFD increased feed conversion and body weight in GF mice independent of the increase associated with the microbiota in CV mice. In contrast to CV mice, GF mice did not decrease feed intake on the HFD and possessed heavier fat pads. The HFD caused hyperglycemia, hyperinsulinemia, and impaired glucose absorption in GF mice independent of the increase associated with the microbiota in CV mice. A HFD also elevated plasma LDL-cholesterol and increased hepatic triacylglycerol, free fatty acids, and ceramides in all mice, whereas hypertriglyceridemia and increased hepatic medium and long-chain acylcarnitines were only observed in CV mice. Therefore, GF male Tac:SW mice developed several detrimental effects of obesity and MetS from a high-fat, calorie dense diet.

Keywords: diet-induced obesity; germ free; gut bacteria; metabolic syndrome; type 2 diabetes.

Abstract

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