1316 Glucose-Induced Glucagon-Like Peptide 1 Secretion Is Deficient in Patients With Non-Alcoholic Fatty Liver Disease

Bernsmeier, Christine; Meyer‐Gerspach, Anne Christin; Blaser, Lea S.; Jeker, L.; Steinert, Robert E.; Heim, Markus H.; Beglinger, C.

doi:10.1016/s0168-8278(13)61317-3

Cited by 1 publication

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References 36 publications

(68 reference statements)

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“…However, insulin tolerance testing is less sensitive than the gold-standard hyperinsulinemic-euglycemic clamp (44)(45)(46), and it should be noted that changes in hepatic insulin sensitivity could be revealed by the tissue-specific nature of a clamp study. Similarly, changes in oral glucose tolerance, which reflects a composite of beta cell function and glucose disposal along with the incretin response, were not detected, which is surprising given that humans with NAFLD have a reduction in secretion of the incretin glucagon-like peptide 1 (GLP-1) (47). Because of the altered incretin response in human NAFLD and the availability of a variety of incretin mimetics for treating type 2 diabetes, more recent research has focused on targeting the incretin system in NASH and potentially repurposing these type 2 diabetes therapeutics for NAFLD and NASH.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of a dietary mouse model of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)

Saenz

McDonough²,

Bloom-Saldana

et al. 2023

Preprint

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Non-alcoholic fatty liver disease (NAFLD), and resultant non-alcoholic steatohepatitis (NASH), incidence and prevalence are rising globally due to increasing rates of obesity and diabetes. Currently, there are no approved pharmacological treatments for NAFLD, highlighting a need for additional mechanistic studies to develop prevention and/or therapeutic strategies. Diet-induced preclinical models of NAFLD can be used to examine the dynamic changes that occur during NAFLD development and progression throughout the lifespan. To date, most studies utilizing such models have focused exclusively on terminal time points and have likely missed critical early and late changes that are important for NAFLD progression (i.e, worsening). We performed a longitudinal analysis of histopathological, biochemical, transcriptomic, and microbiome changes that occurred in adult male mice fed either a control diet or a NASH-promoting diet (high in fat, fructose, and cholesterol) for up to 30 weeks. We observed progressive development of NAFLD in mice fed the NASH diet compared to the control diet. Differential expression of immune-related genes was observed at an early stage of diet-induced NAFLD development (10 weeks) and persisted into the later stages of the disease (20 and 30 weeks). Differential expression of xenobiotic metabolism related genes was observed at the late stage of diet-induced NAFLD development (30 weeks). Microbiome analysis revealed an increased abundance of Bacteroides at an early stage (10 weeks) that persisted into the later stages of the disease (20 and 30 weeks). These data provide insight into the progressive changes that occur during NAFLD/NASH development and progression in the context of a typical Western diet. Furthermore, these data are consistent with what has been reported in patients with NAFLD/NASH, supporting the preclinical use of this diet-induced model for development of strategies to prevent or treat the disease.

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