Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8

Sylvers-Davie, Kelli L.; Davies, Brandon S.J.

doi:10.1152/ajpendo.00195.2021

Cited by 68 publications

(48 citation statements)

References 189 publications

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“…It was previously reported that in WAT, oscillations of Angptl4 expression follow the pattern in BAT albeit with a 5-hour delay [ 40 ], illustrating tissue-specific regulation and a possible prioritization of fuel utilization by BAT prior to wakening [ 40 ]. ANGPTL8 forms a complex with hepatic-derived ANGPTL3 to strengthen its inhibition of LPL, as well as with ANGPTL4 to counteract its inhibitory effect on LPL [ 41 ], therefore the opposing oscillation of Angptl8 may amplify ANGPTL4 activity at its peak and further inhibit it at its nadir. Importantly, ANGPTLs modulate LPL on protein but not mRNA level, instead oscillations of Lpl gene expression may be driven by PPARγ as described above.…”

Section: Resultsmentioning

confidence: 99%

Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue

Eenige

Panhuis

Schönke

et al. 2022

Molecular Metabolism

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Section: Resultsmentioning

confidence: 99%

Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue

Eenige

Panhuis

Schönke

et al. 2022

Molecular Metabolism

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“…Adenoviral overexpression of the ANGPTL8 gene in mice results in an increase in plasma triacylglycerol (TG) levels [ 10 ] and, consistently, ANGPTL8-knockout mice exhibit low TG concentrations [ 11 , 12 ]. In humans, ANGPTL8 interacts with ANGPTL3 or ANGPTL4 to inhibit LPL activity [ 10 , 13 ] and several ANGPTL8 gene variants have been linked to lipid alterations [ 14 , 15 , 16 ]. Interestingly, serum ANGPTL8 concentrations are decreased in several metabolic conditions, such as obesity, T2D or dyslipidemia [ 17 , 18 , 19 ] and increase after bariatric surgery [ 20 ], although contradictory results have been published [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity

Perdomo

Gómez-Ambrosi

Becerril

et al. 2021

IJMS

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Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.

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“…Although individual ANGPTLs have been studied for more than two decades and many apolipoproteins have been studied extensively for several decades, their ability to interact to provide a sophisticated system for regulation of LPL activity has just begun to be appreciated. [ 3,4,214,215 ]…”

Section: Interplay Between Angptls and Apolipoproteinsmentioning

confidence: 99%

“…LPL activity is precisely regulated by many different proteins in order to allow for storage of FA in the adipose tissue as TG in the postprandial state. [ 2–4 ]…”

Section: Introductionmentioning

confidence: 99%

“…

precisely regulated by many different proteins in order to allow for storage of FA in the adipose tissue as TG in the postprandial state. [2][3][4] The ability to efficiently store FA as TG in the adipose tissue in the fed state helped our ancestors survive prolonged periods of caloric insufficiency by ensuring a ready source of stored TG whose FA could be released from the fat into the circulation to provide the energy to skeletal muscle needed to hunt for food. In our modern society, however, immoderate caloric intake may lead to excessive fat storage in adipose tissue, increased circulating TG, and ectopic fat disposition in organs such as the liver.

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confidence: 99%

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The Regulation of Triacylglycerol Metabolism and Lipoprotein Lipase Activity

2022

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Triacylglycerol (TG) metabolism is tightly regulated to maintain a pool of TG within circulating lipoproteins that can be hydrolyzed in a tissue‐specific manner by lipoprotein lipase (LPL) to enable the delivery of fatty acids to adipose or oxidative tissues as needed. Elevated serum TG concentrations, which result from a deficiency of LPL activity or, more commonly, an imbalance in the regulation of tissue‐specific LPL activities, have been associated with an increased risk of atherosclerotic cardiovascular disease through multiple studies. Among the most critical LPL regulators are the angiopoietin‐like (ANGPTL) proteins ANGPTL3, ANGPTL4, and ANGPTL8, and a number of different apolipoproteins including apolipoprotein A5 (ApoA5), apolipoprotein C2 (ApoC2), and apolipoprotein C3 (ApoC3). These ANGPTLs and apolipoproteins work together to orchestrate LPL activity and therefore play pivotal roles in TG partitioning, hydrolysis, and utilization. This review summarizes the mechanisms of action, epidemiological findings, and genetic data most relevant to these ANGPTLs and apolipoproteins. The interplay between these important regulators of TG metabolism in both fasted and fed states is highlighted with a holistic view toward understanding key concepts and interactions. Strategies for developing safe and effective therapeutics to reduce circulating TG by selectively targeting these ANGPTLs and apolipoproteins are also discussed.

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Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8

Cited by 68 publications

References 189 publications

Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue

Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue

Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity

The Regulation of Triacylglycerol Metabolism and Lipoprotein Lipase Activity

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