Hepatic de novo lipogenesis and fat oxidation predict the postprandial response of triglyceride-rich lipoprotein particles in healthy subjects

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver, achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

Download Full-text

Fractional hepatic de novo lipogenesis in healthy subjects during near-continuous oral nutrition and bed rest: a comparison with published data in artificially fed, critically ill patients

Clinical Nutrition ◽

10.1054/clnu.2002.0559 ◽

2002 ◽

Vol 21 (4) ◽

pp. 345-350 ◽

Cited By ~ 3

Author(s):

K. MINEHIRA ◽

L. TAPPY ◽

R. CHIOLERO ◽

V. VLADIMIROVA ◽

M.M. BERGER ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Healthy Subjects ◽

De Novo ◽

Bed Rest ◽

De Novo Lipogenesis ◽

Published Data ◽

Oral Nutrition

Download Full-text

Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.5.e814 ◽

1993 ◽

Vol 265 (5) ◽

pp. E814-E820 ◽

Cited By ~ 9

Author(s):

M. K. Hellerstein ◽

R. A. Neese ◽

J. M. Schwarz

Keyword(s):

Fatty Acids ◽

Free Fatty Acids ◽

De Novo ◽

Human Subjects ◽

Fat Oxidation ◽

De Novo Lipogenesis ◽

Whole Body ◽

Distribution Analysis ◽

Oxidation Rates ◽

Mass Isotopomer Distribution Analysis

We have previously presented a precursor-product stable isotopic technique for measuring in vivo the fraction of very low-density lipoprotein-fatty acids (VLDL-FA) derived from de novo lipogenesis (fractional DNL). Here, we propose a technique for converting fractional DNL into absolute rates of DNL and describe its explicit underlying assumptions. The technique combines the fractional DNL method with a modification of the method of S. Klein, V. R. Young, G. L. A. Blackburn, B. R. Bistrain, and R. R. Wolfe (J. Clin. Invest. 78: 928-933, 1986), for estimating hepatic reesterification of free fatty acids (FFA). Infusions of [1,2,3,4-13C]palmitate and [1-13C]acetate are performed concurrently with indirect calorimetry in human subjects. Fractional DNL (based on mass isotopomer distribution analysis of VLDL-FA), the rate of appearance of plasma FFA (Ra of FFA), and net fat oxidation in the whole body are measured. Equations from the hepatic reesterification model, modified to include the contribution from DNL, allow calculation of absolute DNL (= fractional DNL x [Ra of FFA - net whole body fat oxidation], when respiratory quotient < 1.0). Sample results from human subjects with different dietary energy intakes are presented, with calculations of absolute DNL, absolute reesterification, and absolute fat oxidation rates. The assumptions of this technique (in particular, that all fat oxidized is derived at steady state from circulating FFA and that DNL and reesterification of FFA both occur exclusively in liver) are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation in Vivo

10.20944/preprints201808.0026.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Marc Foretz ◽

Patrick Even ◽

Benoit Viollet

Keyword(s):

Lipid Metabolism ◽

De Novo ◽

Fat Oxidation ◽

De Novo Lipogenesis ◽

Acid Oxidation ◽

Ampk Activation ◽

Hepatic Lipid ◽

Adenoviral Delivery ◽

Body Production

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

Download Full-text

A nutrient cocktail prevents lipid metabolism alterations induced by 20 days of daily steps reduction and fructose overfeeding: result from a randomized study

Journal of Applied Physiology ◽

10.1152/japplphysiol.00018.2018 ◽

2019 ◽

Vol 126 (1) ◽

pp. 88-101 ◽

Cited By ~ 2

Author(s):

Anthony Damiot ◽

Rémi Demangel ◽

John Noone ◽

Isabelle Chery ◽

Alexandre Zahariev ◽

...

Keyword(s):

Lipid Metabolism ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Physical Inactivity ◽

De Novo ◽

Fat Oxidation ◽

De Novo Lipogenesis ◽

Sedentary Behaviors ◽

Protein Ubiquitination ◽

Total Fat

Physical inactivity and sedentary behaviors are independent risk factors for numerous diseases. We examined the ability of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E, and selenium to prevent the expected metabolic alterations induced by physical inactivity and sedentary behaviors. Healthy trained men ( n = 20) (averaging ∼14,000 steps/day and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps (averaging ∼3,000 steps/day). During the last 10 days, metabolic changes were further triggered by fructose overfeeding. On days 0, 10, and 20, body composition (dual energy X-ray), blood chemistry, glucose tolerance [oral glucose tolerance test (OGTT)], and substrate oxidation (indirect calorimetry) were measured. OGTT included 1% fructose labeled with (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and related cellular markers were assessed from muscle biopsies collected on days 0 and 20. While the cocktail did not prevent the decrease in insulin sensitivity and its muscular correlates induced by the intervention, it fully prevented the hypertriglyceridemia, the drop in fasting HDL and total fat oxidation, and the increase in de novo lipogenesis. The cocktail further prevented the decrease in the type-IIa muscle fiber cross-sectional area and was associated with lower protein ubiquitination content. The circulating antioxidant capacity was improved by the cocktail following the OGTT. In conclusion, a cocktail of nutrient compounds from dietary origin protects against the alterations in lipid metabolism induced by physical inactivity and fructose overfeeding. NEW & NOTEWORTHY This is the first study to test the efficacy of a novel dietary nutrient cocktail on the metabolic and physiological changes occurring during 20 days of physical inactivity along with fructose overfeeding. The main findings of this study are that 1) reduction in daily steps leads to decreased insulin sensitivity and total fat oxidation, resulting in hyperlipemia and increased de novo lipogenesis and 2) a cocktail supplement prevents the alterations on lipid metabolism.

Download Full-text