Enhanced triacylglycerol production in oleaginous microalga Neochloris oleoabundans by co-overexpression of lipogenic genes: Plastidial LPAAT1 and ER-located DGAT2

ABSTRACT We used a Cre-loxP approach to generate mice with varied expression of hepatic Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient homeostasis. While nutrient-sensitive transcripts were expressed nearly normally in liver lacking Irs2 (LKO2 mice), these transcripts were significantly dysregulated in liver lacking Irs1 (LKO1 mice) or Irs1 and Irs2 together (DKO mice). Similarly, a set of key gluconeogenic and lipogenic genes was regulated nearly normally by feeding in liver retaining a single Irs1 allele without Irs2 (DKO/1 mice) but was poorly regulated in liver retaining one Irs2 allele without Irs1 (DKO/2 mice). DKO/2 mice, but not DKO/1 mice, also showed impaired glucose tolerance and insulin sensitivity—though both Irs1 and Irs2 were required to suppress hepatic glucose production during hyperinsulinemic-euglycemic clamp. In contrast, either hepatic Irs1 or Irs2 mediated suppression of HGP by intracerebroventricular insulin infusion. After 12 weeks on a high-fat diet, postprandial tyrosine phosphorylation of Irs1 increased in livers of control and LKO2 mice, whereas tyrosine phosphorylation of Irs2 decreased in control and LKO1 mice. Moreover, LKO1 mice—but not LKO2 mice—that were fed a high-fat diet developed postprandial hyperglycemia. We conclude that Irs1 is the principal mediator of hepatic insulin action that maintains glucose homeostasis.

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Revalorization of Neochloris oleoabundans biomass as source of biodiesel by concurrent production of lipids and carotenoids

Algal Research ◽

10.1016/j.algal.2014.05.001 ◽

2014 ◽

Vol 5 ◽

pp. 16-22 ◽

Cited By ~ 20

Author(s):

I. Urreta ◽

Z. Ikaran ◽

I. Janices ◽

E. Ibañez ◽

M. Castro-Puyana ◽

...

Keyword(s):

Neochloris Oleoabundans

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Análise do genoma da microalga produtora de lipídios Neochloris oleoabundans,visando à produção de combustíveis de terceira geração

10.47749/t/unicamp.2013.884744 ◽

2013 ◽

Author(s):

Bruna Roncon Favarelli

Keyword(s):

Neochloris Oleoabundans

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Effect of trans-10, cis-12 conjugated linoleic acid (CLA) on expression of lipogenic genes is related to amount of trans-10, cis-12 CLA per unit of metabolic weight in lactating dairy ewes

Small Ruminant Research ◽

10.1016/j.smallrumres.2018.10.009 ◽

2018 ◽

Vol 169 ◽

pp. 42-45

Author(s):

D.E. Oliveira ◽

M. Urio ◽

E.C. Sandri

Keyword(s):

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Lipogenic Genes ◽

Dairy Ewes

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Impact of exenatide on mitochondrial lipid metabolism in mice with nonalcoholic steatohepatitis

Journal of Endocrinology ◽

10.1530/joe-19-0007 ◽

2019 ◽

Vol 241 (3) ◽

pp. 293-305 ◽

Cited By ~ 7

Author(s):

Srilaxmi Kalavalapalli ◽

Fernando Bril ◽

Joy Guingab ◽

Ariana Vergara ◽

Timothy J Garrett ◽

...

Keyword(s):

Insulin Resistance ◽

G Protein ◽

Nonalcoholic Steatohepatitis ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Tca Cycle ◽

Lipogenic Genes ◽

Relative Contribution ◽

High Fructose ◽

Triglyceride Content

Exenatide (Exe) is a glucagon-like peptide (GLP)-1 receptor agonist that enhances insulin secretion and is associated with induction of satiety with weight loss. As mitochondrial dysfunction and lipotoxicity are central features of nonalcoholic steatohepatitis (NASH), we tested whether Exe improved mitochondrial function in this setting. We studied C57BL/6J mice fed for 24 weeks either a control- or high-fructose, high-trans-fat (TFD)-diet (i.e., a NASH model previously validated by our laboratory). For the final 8 weeks, mice were treated with Exe (30 µg/kg/day) or vehicle. Mitochondrial metabolism was assessed by infusion of [13C3]propionate, [3,4-13C2]glucose and NMR-based 13C-isotopomer analysis. Exenatide significantly decreased fasting plasma glucose, free fatty acids and triglycerides, as well as adipose tissue insulin resistance. Moreover, Exe reduced 23% hepatic glucose production, 15% tri-carboxylic acid (TCA) cycle flux, 20% anaplerosis and 17% pyruvate cycling resulting in a significant 31% decrease in intrahepatic triglyceride content (P = 0.02). Exenatide improved the lipidomic profile and decreased hepatic lipid byproducts associated with insulin resistance and lipotoxicity, such as diacylglycerols (TFD: 111 ± 13 vs Exe: 64 ± 13 µmol/g protein, P = 0.03) and ceramides (TFD: 1.6 ± 0.1 vs Exe: 1.3 ± 0.1 µmol/g protein, P = 0.03). Exenatide lowered expression of hepatic lipogenic genes (Srebp1C, Cd36) and genes involved in inflammation and fibrosis (Tnfa, Timp1). In conclusion, in a diet-induced mouse model of NASH, Exe ameliorates mitochondrial TCA cycle flux and significantly decreases insulin resistance, steatosis and hepatocyte lipotoxicity. This may have significant clinical implications to the potential mechanism of action of GLP-1 receptor agonists in patients with NASH. Future studies should elucidate the relative contribution of direct vs indirect mechanisms at play.

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