Increased lipogenesis in spite of upregulated hepatic 5'AMP‐activated protein kinase in human non‐alcoholic fatty liver

Loeffelholz, Christian von; Döcke, Stephanie; Lock, Johan Friso; Lieske, Stefanie; Horn, Paul; Kriebel, Jennifer; Wahl, Simone; Singmann, Paula; Gala, Tonia de las Heras; Grallert, Harald; Raschzok, Nathanael; Sauer, Igor M.; Heller, Regine; Jahreis, Gerhard; Claus, Ralf A.; Bauer, Michael; Stockmann, Martin; Birkenfeld, Andreas L.; Pfeiffer, Andreas F. H.

doi:10.1111/hepr.12825

Cited by 24 publications

(18 citation statements)

References 54 publications

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“…In addition, palmitate, contained in HFCD, may induce lipogenesis by activating X-Box binding protein-1-mediated endoplasmic reticulum stress, demonstrated by the increase in steatosis score ≥2, associated with blood palmitate (68,69). In the normal rat group, the physiological level of SCD-1 maintained a balanced ratio of MUSFA/SFA to keep the hepatic tissue healthy without fat accumulation.…”

Section: Discussionmentioning

confidence: 99%

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Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

Al‐Muzafar

Amin

2018

Exp Ther Med

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Hepatosteatosis is a disease present worldwide, which presents a number of health problems. Recently, thiazolidinedione (TZD) has been used as a therapy for lipid disorders. The present study demonstrates the potential of TZD as a treatment for hepatosteatosis and its mechanism of action, particularly focusing on its role in lipid metabolism. A total of 60 (80–90 g) rats were divided into three groups: A normal group with a standard diet, a high-fat, high-carbohydrate diet (HFCD) group or a HFCD+TZD group (n=20/group). The HFCD induced hepatosteatosis over a period of 12 weeks and the HFCD+TZD group were administered TZD in weeks 13–16. Blood and tissue samples were collected to measure hepatic function, the lipid profile, metabolism and hormone biomarkers, including serum triglyceride (TG), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD-1), leptin and resistin. The HFCD-fed rats exhibited a significant increase in serum TG, total cholesterol, low-density lipoproteins, alanine transaminase and bilirubin compared with the normal group as well as a significant decrease in high-density lipoprotein. In addition, serum leptin and resistin were significantly elevated in the HFCD group compared with the normal group. The administration of TZD significantly increased SCD-1 activity and significantly inhibited LPL activity. It also attenuated the changes in the lipid profiles and normalized serum leptin and resistin levels. The results of the present study indicated that HFCD induced lipid abnormalities associated with hypertriglyceridemia, hypercholesterolemia and hepatosteatosis. These changes resulted from disruption to leptin and resistin, which may be due to alterations in LPL and SCD-1 activity. TZD mitigated the effects of HFCD-induced hepatosteatosis, indicating a possible regulatory effect of TZD in the development of hepatosteatosis. The authors suggest that the manipulation of SCD-1 and lipase by TZD may be useful as a treatment for hepatosteatosis.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, evidence has indicated that SCD-1 overexpression is associated with liver fibrosis and hepatocellular carcinoma (68,70). In addition, a high fructose diet prolonged hepatic SCD-1 activation and promoted TG accumulation and steatosis (71,72).…”

Section: Discussionmentioning

confidence: 99%

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

Al‐Muzafar

Amin

2018

Exp Ther Med

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“…On the other hand, studies of FAO in patients with or NASH are conflicting, reporting enhanced [118][119][120], unchanged [121], or decreased FAO [122]. The expression of genes related to mitochondrial and peroxisomal β-oxidation was higher in patients with more severe steatosis than in individuals with less severe steatosis or in nonsteatotic controls [123]. Additionally, β-oxidation, measured indirectly as plasma β-hydroxybutyrate levels, was higher in patients with NASH than in those with steatosis or normal controls [120].…”

Section: Fatty Acid Oxidation and Vldl Secretionmentioning

confidence: 98%

Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

et al. 2019

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Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD.

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“…Pharmacological inhibition of sodium-coupled citrate transporter. Slc13a5 deletion and pharmacological inhibition ameliorate obesity, insulin resistance, and NAFLD in various model organisms (Birkenfeld et al, 2011;Shulman and Helfand, 2011;Willmes and Birkenfeld, 2013;Neuschäfer-Rube et al, 2014;Huard et al, 2015;Pesta et al, 2015;Brachs et al, 2016;Willmes et al, 2016Willmes et al, , 2018Rogina, 2017;von Loeffelholz et al, 2017a). NaCT has therefore been proposed as a promising target for the prevention and treatment of metabolic diseases.…”

Section: Skeletal Musclementioning

confidence: 99%

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

et al. 2019

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Increased lipogenesis in spite of upregulated hepatic 5'AMP‐activated protein kinase in human non‐alcoholic fatty liver

Cited by 24 publications

References 54 publications

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

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