Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

Ong, Kuok Teong; Mashek, Mara T.; Davidson, Nicholas O.; Mashek, Douglas G.

doi:10.1194/jlr.m039867

Cited by 38 publications

(28 citation statements)

References 45 publications

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“…This outcome does not agree with the reports of others ( 52,59 ) and may refl ect differences in cell culture models, methods of PPAR activation, or the type of FAs stored as neutral lipid in cells. In this regard, the HFD knocks down the expression of multiple PPAR target genes ( Fig.…”

Section: Faocontrasting

confidence: 52%

“…Cellular levels of ATGL have been associated with changes in PPAR signaling (51)(52)(53)59 ). PPAR activity is sensitive to changes in intracellular FA composition, particularly as NEFA.…”

Section: Infl Uence Of Atgl Expression Of Ppar Signalingmentioning

confidence: 99%

“…Finally, cellular ATGL levels have been linked to PPAR signaling (51)(52)(53)59 ). Some have suggested that ATGL regulates cellular levels of FAs controlling PPAR activity.…”

Section: Faomentioning

confidence: 99%

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Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice

Tripathy

Lytle

Stevens

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org populations. NAFLD is the hepatic manifestation of metabolic syndrome and is associated with a cluster of metabolic risk factors including obesity, dyslipidemia, type 2 diabetes, and hypertension ( 1 ). The prevalence of NAFLD is ‫ف‬ 30% in US adults but is as high as 90-95% in obese individuals and у 60% in type 2 diabetic subjects ( 2 ). NAFLD is viewed as a pathological spectrum with benign fatty liver at one end and nonalcoholic steatohepatitis (NASH; infl ammation, oxidative stress, hepatic damage, and fi brosis) at the other end ( 1 ). Thirty to 40% of individuals with simple fatty liver develop NASH, which can progress to cirrhosis, a risk factor for hepatic cancer ( 3 ).NAFLD involves excessive neutral lipid storage in the liver as TG, cholesteryl ester, and diacylglycerol (DAG) ( 4-6 ). NEFAs used for TG synthesis are derived from multiple sources including those mobilized from adipose tissue, Abstract Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. Nonalcoholic fatty liver disease (NAFLD) is a signifi cant public health concern for the obese and type 2 diabetic

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Section: Faocontrasting

confidence: 52%

“…Cellular levels of ATGL have been associated with changes in PPAR signaling (51)(52)(53)59 ). PPAR activity is sensitive to changes in intracellular FA composition, particularly as NEFA.…”

Section: Infl Uence Of Atgl Expression Of Ppar Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice

Tripathy

Lytle

Stevens

et al. 2014

Journal of Lipid Research

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“…In contrast, WAT Ucp1 mRNA in chow-fed Fgf21 -/-mice was not different from WT, and neither the HFD nor naringenin affected its expression ( Figure 3C). As both adipose triglyceride lipase (ATGL, Pnpla2) and hormone sensitive lipase (HSL, Lipe) can liberate fatty acids, which may indirectly activate a PPAR␣ transcription program, we assessed their mRNA abundance (45,46). Lipe was lower in HFD-fed Fgf21 -/-mice compared to HFD-fed WT mice, consistent with increased adiposity in HFD-fed Fgf21 -/-mice.…”

Section: Enhanced Weight Gain In Hfd-fed Fgf21 -/-Mice Is Prevented Bmentioning

confidence: 69%

Naringenin Prevents Obesity, Hepatic Steatosis, and Glucose Intolerance in Male Mice Independent of Fibroblast Growth Factor 21

et al. 2015

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The molecular mechanisms and metabolic pathways whereby the citrus flavonoid, naringenin, reduces dyslipidemia and improves glucose tolerance were investigated in C57BL6/J wild-type mice and fibroblast growth factor 21 (FGF21) null (Fgf21(-/-)) mice. FGF21 regulates energy homeostasis and the metabolic adaptation to fasting. One avenue of this regulation is through induction of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc1a), a regulator of hepatic fatty acid oxidation and ketogenesis. Because naringenin is a potent activator of hepatic FA oxidation, we hypothesized that induction of FGF21 might be an integral part of naringenin's mechanism of action. Furthermore, we predicted that FGF21 deficiency would potentiate high-fat diet (HFD)-induced metabolic dysregulation and compromise metabolic protection by naringenin. The absence of FGF21 exacerbated the response to a HFD. Interestingly, naringenin supplementation to the HFD robustly prevented obesity in both genotypes. Gene expression analysis suggested that naringenin was not primarily targeting fatty acid metabolism in white adipose tissue. Naringenin corrected hepatic triglyceride concentrations and normalized hepatic expression of Pgc1a, Cpt1a, and Srebf1c in both wild-type and Fgf21(-/-) mice. HFD-fed Fgf21(-/-) mice displayed greater muscle triglyceride deposition, hyperinsulinemia, and impaired glucose tolerance as compared with wild-type mice, confirming the role of FGF21 in insulin sensitivity; however, naringenin supplementation improved these metabolic parameters in both genotypes. We conclude that FGF21 deficiency exacerbates HFD-induced obesity, hepatic steatosis, and insulin resistance. Furthermore, FGF21 is not required for naringenin to protect mice from HFD-induced metabolic dysregulation. Collectively these studies support the concept that naringenin has potent lipid-lowering effects and may act as an insulin sensitizer in vivo.

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“…The enzyme ATGL catalyzes the initial step in triglyceride (TG) hydrolysis in adipocyte lipid droplets (Zimmermann et al, 2004;Arner and Langin, 2007;Chakrabarti et al, 2013). Recent evidence suggests that ATGL also plays an important role in lipid droplet degradation in non-adipocyte cells (Ong et al, 2014). In addition to adipose tissue, the mammary gland is one of the most active metabolic tissues during pregnancy and lactation.…”

Section: Introductionmentioning

confidence: 99%

Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells

Luo

Wang

et al. 2015

Gene

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Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

Cited by 38 publications

References 45 publications

Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice

Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice

Naringenin Prevents Obesity, Hepatic Steatosis, and Glucose Intolerance in Male Mice Independent of Fibroblast Growth Factor 21

Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells

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