scholarly journals Leptin Regulates Peripheral Lipid Metabolism Primarily through Central Effects on Food Intake

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5432-5439 ◽  
Author(s):  
Xavier Prieur ◽  
Y. C. Loraine Tung ◽  
Julian L. Griffin ◽  
I. Sadaf Farooqi ◽  
Stephen O'Rahilly ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Liver Weight ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Mediated Effects ◽  
Expression Of Genes ◽  
Acyl Coenzyme A

The metabolic effects of leptin may involve both centrally and peripherally mediated actions with a component of the central actions potentially independent of alterations in food intake. Ob/ob mice have significant abnormalities in lipid metabolism, correctable by leptin administration. We used ob/ob mice to study the relative importance of the subtypes of actions of leptin (central vs. peripheral; food intake dependent vs. independent) on lipid metabolism. Mice were treated for 3 d with leptin, either centrally [intracerebroventricular (icv)] or peripherally (ip), and compared with mice pair-fed to the leptin-treated mice (PF) and with ad libitum-fed controls (C). All treatment groups (icv, ip, PF) showed indistinguishable changes in liver weight; hepatic steatosis; hepatic lipidemic profile; and circulating free fatty acids, triglycerides, and cholesterol lipoprotein profile. Changes in the expression of genes involved in lipogenesis and fatty acid oxidation in liver, muscle, and white fat were broadly similar in ip, icv, and PF groups. Leptin (both icv and ip) stimulated expression of both mitochondrial and peroxisomal acyl-coenzyme A oxidase (liver) and peroxisomal proliferator-activated receptor-α (skeletal muscle) to an extent not replicated by pair feeding. Leptin had profound effects on peripheral lipid metabolism, but the majority were explained by its effects on food intake. Leptin had additional centrally mediated effects to increase the expression of a limited number of genes concerned with fatty acid oxidation. Whereas we cannot exclude direct peripheral effects of leptin on certain aspects of lipid metabolism, we were unable to detect any such effects on the parameters measured in this study.

Fatty acid oxidation and glucose utilization interact to control food intake in rats

1986 ◽  
Vol 251 (5) ◽  
pp. R840-R845 ◽  
Author(s):  
M. I. Friedman ◽  
M. G. Tordoff
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Combined Treatment ◽  
Fat Metabolism ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Control Food ◽  
Control Food Intake

To determine whether glucose and fat metabolism interact to control food intake, rats were administered 2-deoxyglucose (2-DG), which inhibits glucose utilization, and methyl palmoxirate (MP), which inhibits fatty acid oxidation. Combined treatment with 2-DG and MP increased food intake in a synergistic fashion. This synergistic effect was observed even at doses of the two agents that alone did not increase food intake, and it was expressed by either an initiation of eating or a prolonged bout of eating, depending on the testing conditions. Metabolic measures of circulating substrates, liver glycogen, and gastric contents confirmed that the drugs had their intended metabolic effects and revealed no evidence that one drug enhanced the direct metabolic action of the other. The results provide direct evidence that glucose and fat metabolism exert a coordinated control over feeding behavior and suggest the existence of a common integrative mechanism in that control.

scholarly journals Interplay between Thyroid Hormones and Stearoyl-CoA Desaturase 1 in the Regulation of Lipid Metabolism in the Heart

2020 ◽  
Vol 22 (1) ◽  
pp. 109
Author(s):  
Adam Olichwier ◽  
Volodymyr V. Balatskyi ◽  
Marcin Wolosiewicz ◽  
James M. Ntambi ◽  
Pawel Dobrzyn
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Thyroid Hormones ◽  
Fatty Acid Oxidation ◽  
Monounsaturated Fatty Acids ◽  
Thyroid Stimulating Hormone ◽  
Acid Oxidation ◽  
Expression Of Genes ◽  
Triglyceride Content ◽  
Stearoyl Coa Desaturase

Stearoyl-CoA desaturase 1 (SCD1), an enzyme that is involved in the biosynthesis of monounsaturated fatty acids, induces the reprogramming of cardiomyocyte metabolism. Thyroid hormones (THs) activate both lipolysis and lipogenesis. Many genes that are involved in lipid metabolism, including Scd1, are regulated by THs. The present study used SCD1 knockout (SCD1−/−) mice to test the hypothesis that THs are important factors that mediate the anti-steatotic effect of SCD1 downregulation in the heart. SCD1 deficiency decreased plasma levels of thyroid-stimulating hormone and thyroxine and the expression of genes that regulate intracellular TH levels (i.e., Slc16a2 and Dio1-3) in cardiomyocytes. Both hypothyroidism and SCD1 deficiency affected genomic and non-genomic TH pathways in the heart. SCD1 deficiency is known to protect mice from genetic- or diet-induced obesity and decrease lipid content in the heart. Interestingly, hypothyroidism increased body adiposity and triglyceride and diacylglycerol levels in the heart in SCD1−/− mice. The accumulation of triglycerides in cardiomyocytes in SCD1−/− hypothyroid mice was caused by the activation of lipogenesis, which likely exceeded the upregulation of lipolysis and fatty acid oxidation. Lipid accumulation was also observed in the heart in wildtype hypothyroid mice compared with wildtype control mice, but this process was related to a reduction of triglyceride lipolysis and fatty acid oxidation. We also found that simultaneous SCD1 and deiodinase inhibition increased triglyceride content in HL-1 cardiomyocytes, and this process was related to the downregulation of lipolysis. Altogether, the present results suggest that THs are an important part of the mechanism of SCD1 in cardiac lipid utilization and may be involved in the upregulation of energetic metabolism that is associated with SCD1 deficiency.

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

2009 ◽  
Vol 296 (4) ◽  
pp. E812-E819 ◽  
Author(s):  
Woo Sik Kim ◽  
Yun Sok Lee ◽  
Seung Hun Cha ◽  
Hyun Woo Jeong ◽  
Sung Sik Choe ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
Energy Homeostasis ◽  
Liver Weight ◽  
Whole Body ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Expression Of Genes ◽  
Ampk Activity

AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, it has been demonstrated that berberine (BBR) exerts antiobesity and antidiabetic effects in obese and diabetic rodent models through the activation of AMPK in peripheral tissues. Here we show that BBR improves lipid dysregulation and fatty liver in obese mice through central and peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, intracerebroventricular administration of BBR decreased the level of malonyl-CoA and stimulated the expression of fatty acid oxidation genes in skeletal muscle. Together, these data suggest that BBR would improve fatty liver in obese subjects, which is probably mediated not only by peripheral AMPK activation but also by neural signaling from the central nervous system.

scholarly journals Mouse Cardiac Acyl Coenzyme A Synthetase 1 Deficiency Impairs Fatty Acid Oxidation and Induces Cardiac Hypertrophy

2011 ◽  
Vol 31 (6) ◽  
pp. 1252-1262 ◽  
Author(s):  
J. M. Ellis ◽  
S. M. Mentock ◽  
M. A. DePetrillo ◽  
T. R. Koves ◽  
S. Sen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cardiac Hypertrophy ◽  
Fatty Acid Oxidation ◽  
Coenzyme A ◽  
Acid Oxidation ◽  
Acyl Coenzyme A

scholarly journals Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism

2017 ◽  
Vol 312 (1) ◽  
pp. E11-E18 ◽  
Author(s):  
Anantha Metlakunta ◽  
Wan Huang ◽  
Maja Stefanovic-Racic ◽  
Nikolaos Dedousis ◽  
Ian Sipula ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Kupffer Cells ◽  
Liver Lipid ◽  
Myeloid Cell ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Acute Effects ◽  
Peripheral Tissues ◽  
Liver Lipid Metabolism

Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin.

scholarly journals Maternal obesity alters placental lysophosphatidylcholines, lipid storage, and the expression of genes associated with lipid metabolism‡

2020 ◽  
Author(s):  
Katie L Bidne ◽  
Alana L Rister ◽  
Andrea R McCain ◽  
Brianna D Hitt ◽  
Eric D Dodds ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Maternal Obesity ◽  
Nutrient Transport ◽  
Digital Pcr ◽  
Lipid Profiles ◽  
Lipid Storage ◽  
Acid Oxidation ◽  
Expression Of Genes

Abstract Dyslipidemia is a characteristic of maternal obesity and previous studies have demonstrated abnormalities in fatty acid oxidation and storage in term placentas. However, there is little information about the effect of pre-pregnancy obesity on placental lipid metabolism during early pregnancy. The objective of this study was to determine the relationship between lipid profiles and markers of metabolism in placentas from obese and lean dams at midgestation. Mice were fed a western diet (WD) or normal diet (ND) and lysophosphatidylcholines (LPCs) and/or phosphatidylcholines (PCs) were measured in dam circulation and placenta sections using liquid chromatography–tandem mass spectrometry and mass spectrometry imaging, respectively. In WD dam, circulating LPCs containing 16:1, 18:1, 20:0, and 20:3 fatty acids were increased and 18:2 and 20:4 were decreased. In WD placenta from both sexes, LPC 18:1 and PC 36:1 and 38:3 were increased. Furthermore, there were moderate to strong correlations between LPC 18:1, PC 36:1, and PC 38:3. Treatment-, spatial-, and sex-dependent differences in LPC 20:1 and 20:3 were also detected. To identify genes that may regulate diet-dependent differences in placenta lipid profiles, the expression of genes associated with lipid metabolism and nutrient transport was measured in whole placenta and isolated labyrinth using droplet digital PCR and Nanostring nCounter assays. Several apolipoproteins were increased in WD placentas. However, no differences in nutrient transport or fatty acid metabolism were detected. Together, these data indicate that lipid storage is increased in midgestation WD placentas, which may lead to lipotoxicity, altered lipid metabolism and transport to the fetus later in gestation.

scholarly journals Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic Very Low-Density Lipoprotein Production in Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2169-2174 ◽  
Author(s):  
Wan Huang ◽  
Anantha Metlakunta ◽  
Nikolas Dedousis ◽  
Heidi K. Ortmeyer ◽  
Maja Stefanovic-Racic ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Saline Control ◽  
Acid Oxidation ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Vldl Metabolism

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P < 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P < 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P < 0.01), increased liver TGs (∼20%, P < 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P < 0.01) and increased fatty acid oxidation (∼50%, P < 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles.

Influence of ketone body and the inhibition of fatty acid oxidation on the food intake of the chick

2001 ◽  
Vol 42 (3) ◽  
pp. 405-408 ◽  
Author(s):  
K. Sashihara ◽  
M. Miyamoto ◽  
A. Ohgushi ◽  
D.M. Denbow ◽  
M. Furuse
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Ketone Body ◽  
Acid Oxidation
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