Chiara H Moretti1, Tomas A Schiffer1, Xuechen Li1,2, Eddie Weitzberg1,3, Mattias Carlström1, Jon O Lundberg1. 1. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 2. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. 3. Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Abstract
AIM: Studies in the past 15 years have highlighted the role of the gut microbiota in modulation of host metabolism. The observation that germ-free (GF) mice are leaner than conventionally raised (CONV) mice and their apparent resistance to diet-induced obesity (DIO), sparked the interest in dissecting the possible causative role of the gut microbiota in obesity and metabolic diseases. However, discordant results among studies leave such relationship elusive. In this study, we compared the effects of chronic Western diet (WD) intake on body weight and metabolic function of GF and CONV mice. METHODS: We fed GF and CONV mice a WD for 16 weeks and monitored body weight weekly. At the end of the dietary challenge, the metabolic phenotype of the animals was assessed. Muscle carnitine palmitoyltransferase I (CPT1) and liver AMPK activation were investigated. RESULTS: Both GF and CONV mice gained weight and developed glucose intolerance when fed a WD. Moreover, WD feeding was associated with increased adipose tissue inflammation, repressed hepatic AMPK activity, fatty liver and elevated hepatic triglycerides in both groups of mice. Enhanced fatty acid oxidation in the GF mouse is one of the proposed mechanisms for their resistance to DIO. The GF mice in this study showed higher CPT1 activity as compared to their CONV counterparts, despite not being protected from obesity. CONCLUSIONS: We provide evidence that the microbiota is not an indispensable factor in the onset of obesity and metabolic dysfunction, suggesting that the relationship between gut bacteria and metabolic diseases needs further exploration.
AIM: Studies in the past 15 years have highlighted the role of the gut microbiota in modulation of host metabolism. The observation that germ-free (GF) mice are leaner than conventionally raised (CONV) mice and their apparent resistance to diet-induced obesity (DIO), sparked the interest in dissecting the possible causative role of the gut microbiota in obesity and metabolic diseases. However, discordant results among studies leave such relationship elusive. In this study, we compared the effects of chronic Western diet (WD) intake on body weight and metabolic function of GF and CONV mice. METHODS: We fed GF and CONV mice a WD for 16 weeks and monitored body weight weekly. At the end of the dietary challenge, the metabolic phenotype of the animals was assessed. Muscle carnitine palmitoyltransferase I (CPT1) and liver AMPK activation were investigated. RESULTS: Both GF and CONV mice gained weight and developed glucose intolerance when fed a WD. Moreover, WD feeding was associated with increased adipose tissue inflammation, repressed hepatic AMPK activity, fatty liver and elevated hepatic triglycerides in both groups of mice. Enhanced fatty acid oxidation in the GF mouse is one of the proposed mechanisms for their resistance to DIO. The GF mice in this study showed higher CPT1 activity as compared to their CONV counterparts, despite not being protected from obesity. CONCLUSIONS: We provide evidence that the microbiota is not an indispensable factor in the onset of obesity and metabolic dysfunction, suggesting that the relationship between gut bacteria and metabolic diseases needs further exploration.
Authors: Andrew K Benson; Scott A Kelly; Ryan Legge; Fangrui Ma; Soo Jen Low; Jaehyoung Kim; Min Zhang; Phaik Lyn Oh; Derrick Nehrenberg; Kunjie Hua; Stephen D Kachman; Etsuko N Moriyama; Jens Walter; Daniel A Peterson; Daniel Pomp Journal: Proc Natl Acad Sci U S A Date: 2010-10-11 Impact factor: 11.205
Authors: Marie A Hildebrandt; Christian Hoffmann; Scott A Sherrill-Mix; Sue A Keilbaugh; Micah Hamady; Ying-Yu Chen; Rob Knight; Rexford S Ahima; Frederic Bushman; Gary D Wu Journal: Gastroenterology Date: 2009-08-23 Impact factor: 22.682
Authors: M Poggi; D Bastelica; P Gual; M A Iglesias; T Gremeaux; C Knauf; F Peiretti; M Verdier; I Juhan-Vague; J F Tanti; R Burcelin; M C Alessi Journal: Diabetologia Date: 2007-04-11 Impact factor: 10.122
Authors: Teayoun Kim; Lan He; Maria S Johnson; Yan Li; Ling Zeng; Yishu Ding; Qinqiang Long; John F Moore; Jon D Sharer; Tim R Nagy; Martin E Young; Philip A Wood; Qinglin Yang Journal: J Diabetes Metab Date: 2014-04-01
Authors: Thomas D Horvath; Faith D Ihekweazu; Sigmund J Haidacher; Wenly Ruan; Kristen A Engevik; Robert Fultz; Kathleen M Hoch; Ruth Ann Luna; Numan Oezguen; Jennifer K Spinler; Anthony M Haag; James Versalovic; Melinda A Engevik Journal: iScience Date: 2022-03-25
Authors: Piero Portincasa; Leonilde Bonfrate; Mohamad Khalil; Maria De Angelis; Francesco Maria Calabrese; Mauro D'Amato; David Q-H Wang; Agostino Di Ciaula Journal: Biomedicines Date: 2021-12-31
Authors: Chiara H Moretti; Tomas A Schiffer; Xuechen Li; Eddie Weitzberg; Mattias Carlström; Jon O Lundberg Journal: Acta Physiol (Oxf) Date: 2020-12-06 Impact factor: 6.311