Insulin Regulation of Hepatic Lipid Homeostasis

Uehara, Kahealani; Santoleri, Dominic; Whitlock, Anna E. Garcia; Titchenell, Paul M.

doi:10.1002/cphy.c220015

Cited by 24 publications

(6 citation statements)

References 350 publications

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“…An additional observation was that decreasing liver sialic acid production causes a decrease in plasma TG in the fed state. Although this may be due to the observed decrease in insulin signaling in the liver, because insulin promotes de novo lipid synthesis in the postprandial state [ 47 , 56 ], its basis is still to be determined.…”

Section: Discussionmentioning

confidence: 99%

Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle

Peng,

Yu,

Huang

et al. 2023

Molecular Metabolism

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Section: Discussionmentioning

confidence: 99%

Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle

Peng,

Yu,

Huang

et al. 2023

Molecular Metabolism

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“…In the presence of IR, patients exhibit enhanced hepatic lipid synthesis and impaired suppression of hepatic glucose production by insulin. Consequently, this dysregulation contributes to the development of hyperglycemia and hypertriglyceridemia in affected individuals [31].…”

Section: Possible Mechanisms Of Resistance Affecting Outcomes In Pati...mentioning

confidence: 99%

Association between triglyceride-glucose index and mortality in patients with cirrhosis: a retrospective cohort study

2024

Preprint

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Background Insulin resistance is common in patients with end-stage chronic liver diseases, especially cirrhosis. The association between the triglyceride glucose (TyG) index, a reliable measure for surrogate marker for insulin resistance, and mortality among cirrhotic patients remains unclear. Methods This retrospective cohort study was based on the MIMIC-IV database. Adult cirrhotic patients were categorized into two groups based on the TyG index: the Q1 group (TyG index < 8.8) and the Q2 group (TyG index ≥ 8.8). The primary outcome was 28-day mortality, and the secondary outcome was in-hospital mortality. COX proportional hazards model analyses were used to investigate the association between TyG index and mortality. Results The study included 1322 patients. The 28-day mortality was 17.9% in the Q1 group and 23.3% in the Q2 group. As categorical variable, elevated TyG index was associated with higher 28-day mortality (HR 1.422, 95% CI 1.098–1.841, P = 0.008) and in-hospital mortality (HR 1.442, 95% CI 1.118–1.859, P = 0.005). As continuous variable, every 1 unit increase in the TyG index was associated with increased 28-day mortality (HR 1.301, 95% CI 1.105–1.531, P = 0.002) and in-hospital mortality (HR 1.345, 95% CI 1.105–1.531, P < 0.001). Conclusions The TyG index was associated with increased mortality among patients with cirrhosis.

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“…Therefore, a comprehensive understanding and integrated approach to prevention and control are imperative. In the context of glucose and lipid metabolic disorders, insulin resistance (IR) can perpetuate itself through a negative feedback loop, leading to hyperinsulinemia and hyperglycemia [ 4 ]. Within the state of IR, the inhibitory effect of insulin on lipolysis is significantly attenuated, resulting in the substantial release of Free Fatty Acids (FFAs) into systemic circulation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway

Lv,

Liu,

Chen

et al. 2024

Antioxidants

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Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

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Insulin Regulation of Hepatic Lipid Homeostasis

Cited by 24 publications

References 350 publications

Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle

Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle

Association between triglyceride-glucose index and mortality in patients with cirrhosis: a retrospective cohort study

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway

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