In vivo and in vitro lipogenesis and aspects of metabolism in ovines: Effect of environmental temperature and dietary lipid supplementation

Twenty-four wether lambs were randomly allocated to six treatments to investigate the effect of temperature and dietary lipid supplements on fatty acid synthesis and metabolic activity in sheep. The treatments consisted of four groups exposed to either cold (0 °C) or warm temperature (+23 °C) and given ad libitum access to either a control barley-based diet or with lipid supplementation. Two other groups were placed on the dietary regimen at 0 °C, but pair-fed to intake of animals in the +23 °C environment. At 5 wk, fatty acid synthesis was measured by [1-14C]acetate incorporation into tissue lipids. Cold exposure and dietary lipid supplementation had no effect (P > 0.05) on in vivo fatty acid synthesis rates in either longissimus dorsi or the liver. In both subcutaneous and mesenteric adipose tissue depots, the rate of acetate incorporation into tissue lipid was not significantly affected by cold exposure. In the perirenal fat depot, cold exposure increased (P < 0.05) the rate of fatty acid synthesis, while lipid supplementation decreased (P < 0.05) the rate in all tissue adipose depots. In vitro, mesenteric and perirenal adipose tissues from cold pair-fed animals had higher (P < 0.05) rates of fatty acid synthesis compared to tissues from animals in the warm environment. However, there was no effect of dietary lipid supplementation in these two fat depots. Metabolic heat production, and energy and nitrogen excretion by animals were increased (P < 0.05) by cold exposure while lipid supplementation had the opposite effect (P < 0.05). The relationship between average daily gain and feed intake was linear at both warm and cold environments, but with higher (P < 0.05) average daily gain at all levels of intake in the cold compared to the warm environment. Results indicate that both environment and diet regulate metabolic activity in sheep. However, there were differences in lipogenic response by tissues to the treatments. Key words: Environmental temperature, dietary lipid, fatty acid synthesis, metabolic rate, sheep

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Effect of dietary fructose on in vitro and in vivo fatty acid synthesis in the rat

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(74)90175-1 ◽

1974 ◽

Vol 360 (1) ◽

pp. 1-11 ◽

Cited By ~ 38

Author(s):

Dale R. Romsos ◽

Gilbert A. Leveille

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Dietary Fructose

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USP22-dependent accumulation of lipidomes drives hepatocellular carcinoma progression by stabilizing PPARγ

10.21203/rs.3.rs-82450/v1 ◽

2020 ◽

Author(s):

Zhen Ning ◽

Xin Guo ◽

Xiaolong Liu ◽

Chang Lu ◽

Aman Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Fatty Acid ◽

Molecular Mechanism ◽

Fatty Acid Synthesis ◽

De Novo ◽

Acid Synthesis ◽

Specific Protease ◽

Pparγ Expression

Abstract Elevated de novo lipogenesis (DNL) is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. However, the molecular mechanism for its occurrence in HCC is still unclear. Herein, we identified ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with, deubiquitinates and stabilizes PPARγ through K48-linked deubiquitination, and in turn, this stabilization increases ACC and ACLY transcription. In addition, we found that USP22 promoted the de novo synthesis of fatty acid labeling from glucose tracers. USP22-dysregulated de novo fatty acid synthesis contributes to HCC progression, but USP22 was functionality suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vitro cell proliferation and in vivo tumorigenesis experiments. In HCC, USP22 expression positively correlates with PPARγ expression, and simultaneously, high expression of USP22 and PPARγ or USP22, ACC and ACLY is associated with a poor prognosis. Taken together, we identified a previously undescribed USP22-regulated lipogenesis molecular mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition.

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Glucagon regulates ACC activity in adipocytes through the CAMKKβ/AMPK pathway

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00504.2011 ◽

2012 ◽

Vol 302 (12) ◽

pp. E1560-E1568 ◽

Cited By ~ 23

Author(s):

I-Chen Peng ◽

Zhen Chen ◽

Wei Sun ◽

Ying-Shiuan Li ◽

Traci LaNai Marin ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Protein Kinase ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Dependent Protein Kinase ◽

Ampk Signaling ◽

Dependent Protein

Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser79, an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca2+/calmodulin-dependent protein kinase kinase-β knockout (CaMKKβ−/−) mice and cultured adipocytes, we further show that glucagon activates the CaMKKβ/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKβ+/+ but not CaMKKβ−/− mice. These results indicate that CaMKKβ/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage.

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Regulation of lipogenesis. Stimulation of fatty acid synthesis in vivo and in vitro in the liver of the newly hatched chick

Biochemical Journal ◽

10.1042/bj1180259 ◽

1970 ◽

Vol 118 (2) ◽

pp. 259-263 ◽

Cited By ~ 23

Author(s):

Alan G. Goodridge

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Latent Form ◽

Triose Phosphate ◽

Liver Slices ◽

Stimulation Of

1. A single glucose meal stimulated the incorporation of acetate into fatty acids in liver slices. If the glucose was added in vitro, it had no effect. Fructose and glycerol in vitro markedly stimulated fatty acid synthesis from acetate. Fructose and glycerol probably by-passed a rate-controlling reaction between glucose and triose phosphate. This reaction may have been stimulated by glucose administered in vivo. 2. The stimulation of fatty acid synthesis caused by fructose did not require the synthesis of enzyme, thus indicating that fatty acid-synthesizing enzymes were present in a latent form in the livers from unfed chicks.

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