A Dose-Response Elevation in Hepatic Glucose Uptake is Paralleled by Liver Triglyceride Synthesis and Release

Guiducci, Letizia; Lionetti, Vincenzo; Burchielli, Silvia; Simi, Claudia; Masi, Stefano; Liistro, Tiziana; Pardini, S.; Porciello, C; Cecco, Pietro Di; Vettor, Roberto; Calcagno, Alessandra; Ciociaro, Demetrio; Recchia, Fabio A.; Salvadori, Piero A.; Iozzo, Patricia

doi:10.3109/07435800.2010.534751

Cited by 5 publications

(5 citation statements)

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“…HGU and EGP are dependent on the changing insulin and glucose levels, and chronic hyperglycemia and hyperinsulinemia are commonly present. For example, PET imaging studies in minipigs underscore the relevance of circulating glucose by showing that hyperglycemic- compared with euglycemic-hyperinsulinemia enhanced HGU, hepatic triglyceride content and triglyceride release in proportion to glycemia[ 138 ]. The euglycemic clamp thus provides relevant information on the sole action of insulin on tissue metabolism, being insufficient to characterize the more complex relationship between glucose and lipid metabolism occurring in the liver in real life.…”

Section: Disease Monitoring By Digital Imaging: Focus On Pet and Mechanistic Understandingmentioning

confidence: 99%

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Rebelos¹,

Iozzo²,

Guzzardi³

et al. 2021

WJG

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Metabolic associated fatty liver disease (MAFLD), formerly named “nonalcoholic fatty liver disease” occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death, such as cardiovascular, digestive, metabolic, neoplastic and neuro-degenerative diseases. However, progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation, which acts as disease accelerator. Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver, where insulin resistance has been assumed to play an important role. Special emphasis has been given to digital imaging studies and in particular to positron emission tomography, as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism. An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver, dysregulated endogenous glucose production and insulin resistance.

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Section: Disease Monitoring By Digital Imaging: Focus On Pet and Mechanistic Understandingmentioning

confidence: 99%

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Rebelos¹,

Iozzo²,

Guzzardi³

et al. 2021

WJG

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“…Our results show that HFD off are born with hepatic glucose hypermetabolism, likely depending on their hyperglycemic state. From previous studies, we know that GU in the liver promotes lipid accumulation [39]. In fact, liver lipid accumulation was observed from birth to adult age in our HFD off , in which the frequency of intra-hepatocyte triglyceride vesicles was 4-5 folds higher than in ND off .…”

Section: Discussionmentioning

confidence: 62%

Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model

et al. 2021

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Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.

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“…When the liver accumulates fat, its gluconeogenesis strengthens, resulting in increased blood sugar, hyperglycemia can stimulate increased insulin secretion, causing hyperinsulinemia, which further promotes liver synthesis of TG aggravates the lipid deposition of the liver and forms a vicious circle. [51] Hyper TG causes increased release of free fatty acids, which interferes with the binding of insulin to receptors in the surrounding tissues, resulting in insulin resistance. [52] TC refers to the cholesterol contained in various lipoproteins in serum which including he sum of bound cholesterol and free cholesterol.…”

Section: Relatedmentioning

confidence: 99%

Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology

et al. 2022

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Background: Whether metformin is related to nonalcoholic fatty liver disease (NAFLD) is controversial. Our aim was to investigate the relationship between metformin and NAFLD that may predict the metformin potential of these lesions and new prevention strategies in NAFLD patients.Methods: The meta-analysis was analyzed by Revman 5.3 softwares systematically searched for works published through July 29, 2022. Network pharmacology research based on databases, Cytoscape 3.7.1 software and R software respectively. Results:The following variables were associated with metformin in NAFLD patients: decreased of alanine aminotransferase (ALT) level (mean difference [MD] = −10.84, 95% confidence interval [CI] = −21.85 to 0.16, P = .05); decreased of aspartate amino transferase (AST) level (MD = −4.82, 95% CI = −9.33 to −0.30, P = .04); decreased of triglyceride (TG) level (MD = −0.17, 95% CI = −0.26 to −0.08, P = .0002); decreased of total cholesterol (TC) level (MD = −0.29, 95% CI = −0.47 to −0.10, P = .003); decreased of insulin resistance (IR) level (MD = −0.42, 95% CI = −0.82 to −0.02, P = .04). In addition, body mass index (BMI) (MD = −0.65, 95% CI = −1.46 to 0.16, P = .12) had no association with metformin in NAFLD patients. 181 metformin targets and 868 NAFLD disease targets were interaction analyzed, 15 core targets of metformin for the treatment of NAFLD were obtained. The effect of metformin on NAFLD mainly related to cytoplasm and protein binding, NAFLD, hepatitis B, pathway in cancer, toll like receptor signaling pathway and type 2 diabetes mellitus (T2DM). The proteins of hypoxia inducible factor-1 (HIF1A), nuclear factor erythroid 2-related factor (NFE2L2), nitric oxide synthase 3 (NOS3), nuclear receptor subfamily 3 group C member 1 (NR3C1), PI3K catalytic subunit alpha (PIK3CA), and silencing information regulator 2 related enzyme 1 (SIRT1) may the core targets of metformin for the treatment of NAFLD. Conclusion:Metformin might be a candidate drug for the treatment of NAFLD which exhibits therapeutic effect on NAFLD patients associated with ALT, AST, TG, TC and IR while was not correlated with BMI. HIF1A, NFE2L2, NOS3, NR3C1, PIK3CA, and SIRT1 might be core targets of metformin for the treatment of NAFLD.Abbreviations: ALT = alanine aminotransferase, AST = aspartate amino transferase, BMI = body mass index, CI = confidence interval, HCC = hepatocellular carcinoma, HIF1A = hypoxia inducible factor-1, HOMA-IR = insulin resistance index, IR = insulin resistance, MCC = maximal clique centrality, MD = mean difference, NAFLD = nonalcoholic fatty liver disease, NAFL = nonalcoholic fatty liver, NASH = nonalcoholic steatohepatitis, NFE2L2 = nuclear factor erythroid 2-related factor, NOS = Newcastle-Ottawa quality assessment scale, NOS3 = nitric oxide synthase 3, NR3C1 = nuclear receptor subfamily 3 group C member 1, OR = odds ratio, PIK3CA = PI3K catalytic subunit alpha, PPI = protein protein interaction, SIRT1 = silencing information regulator 2 related enzyme 1, T2DM = type 2 diabetes mellitus, TC = total choleste...

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A Dose-Response Elevation in Hepatic Glucose Uptake is Paralleled by Liver Triglyceride Synthesis and Release

Abstract: A short-term elevation in circulating glucose levels within the physiological postprandial range was sufficient to increase HGU, resulting in a significant synthesis and release of TG by the liver, which was accompanied by an acute rise in γ-GT and liver fat content.

Cited by 5 publications

References 24 publications

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model

Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology

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