Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise

1990 ◽  
Vol 258 (2) ◽  
pp. E382-E389 ◽  
Author(s):  
R. R. Wolfe ◽  
S. Klein ◽  
F. Carraro ◽  
J. M. Weber

We have investigated the role of triglyceride-fatty acid cycling in amplifying control of the net flux of fatty acids in response to exercise and in recovery from exercise. Five normal volunteers were infused with [1-13C]palmitate and D-5-glycerol throughout rest, 4 h of treadmill exercise at 40% maximum O2 consumption, and 2 h of recovery. Total fat oxidation was quantified by indirect calorimetry. Lipolysis (rate of appearance of glycerol) increased from 2.1 +/- 0.3 to 6.0 +/- 1.2 mumol.kg-1.min-1 after 30 min of exercise and progressively increased thereafter to a value of 10.5 +/- 0.8 mumol.kg-1.min-1 after 4 h. Lipolysis decreased rapidly during the first 20 min of recovery, but it was still significantly elevated after 2 h of recovery. The rate of appearance of free fatty acids followed the same pattern of response. Seventy percent of released fatty acids were reesterified at rest, and this value decreased to 25% within the first 30 min of exercise. Reesterification remained less than 35% of lipolysis until the start of recovery, at which time the value rose to 90%. In exercise, more than one-half the increase in fat oxidation could be attributed to the reduction in the percent reesterification. Most of the change in percent reesterification during exercise and recovery was caused by changes in extracellular cycling of fatty acids released into plasma. We conclude that triglyceride-fatty acid cycling plays an important role in enabling a rapid response of fatty acid metabolism to major changes in energy metabolism.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.


2007 ◽  
Vol 32 (6) ◽  
pp. 1008-1024 ◽  
Author(s):  
Lindsay E. Robinson ◽  
Andrea C. Buchholz ◽  
Vera C. Mazurak

Metabolic syndrome (MetS) comprises an array of metabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and glucose intolerance. Individuals with MetS are at elevated risk for diabetes and cardiovascular disease. Central to the etiology of MetS is an interrelated triad comprising inflammation, abdominal obesity, and aberrations in fatty acid metabolism, coupled with the more recently recognized changes in metabolism during the postprandial period. We review herein preliminary evidence regarding the role of dietary n-3 polyunsaturated fatty acids in modulating each of the components of the triad of adiposity, inflammation, and fatty acid metabolism, with particular attention to the role of the postprandial period as a contributor to the pathophysiology of MetS.


2019 ◽  
Vol 122 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Nikos Koundouros ◽  
George Poulogiannis

AbstractA common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K–AKT–mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Cara Dooley ◽  
Alice Ryan

Abstract Objectives The aim of the study was to examine the role of dietary consumption of different types of fatty acids on metabolic risk factors and regional fat deposition in older men and women. We hypothesized that saturated fatty acid (SFA) intake, ratio of monounsaturated fatty acids (MUFA) to polyunsaturated fatty acids (PUFA), and total fat intake, as well as proportion of energy derived from fat, would be associated with markers of insulin resistance, hyperlipidemia, and ectopic fat. Methods Sedentary, obese (Body Mass Index: 29–48 kg/m2) adults (N = 20) aged 45–78 years underwent two-hour oral glucose tolerance test, blood draw, DXA scan, and CT scan of the abdomen and mid-thigh. Seven-day diet records were analyzed with NutritionistPro software and the USDA Foodapedia feature of the Supertracker program. Results Subjects had low fitness levels (VO2 max = 23.5 ±2.4 mL/kg/min) and high total body fat (43.5 ± 1.7%) with abdominal obesity (visceral adipose tissue area = 192.4 ± 18 cm2, subcutaneous abdominal adipose area = 465.4 ± 29 cm2) and intermuscular adipose tissue (IMAT) area in thigh (150.1 ± 17 cm2). The average macronutrient composition of the diet was high in fat (fat as a % of total kcal = 35.5) with SFA, MUFA, and PUFA were respectively represented as 33.0, 34.8, and 22.1% of total fat intake. The average MUFA to PUFA ratio was 1.66. There were no differences in fatty acid intake between subjects with normal glucose tolerance and impaired glucose tolerance subjects. The ratio of MUFA to PUFA was positively correlated with higher fasting glucose (r = 0.42, P = 0.06), glucose intolerance (r = 0.43, P = 0.06), and serum cholesterol (r = 0.48, P = 0.03). PUFA intake as a percentage of fat intake was associated with lower serum cholesterol (r = –0.44, P = 0.05). Associations between diet composition with body composition (abdominal fat, IMAT) were not found to be uniformly significant among a homogenous sample of obese, sedentary subjects with diets high in proportion of lipid. Conclusions Dietary fatty acid intake, specifically MUFA unbalanced by PUFA, was associated with glucose intolerance and increased serum cholesterol, and therefore may confer increased risk for diabetes among obese, sedentary individuals. Future investigation of food sources, or context of dietary lipids, could lead to individualized dietary recommendations to promote healthy eating habits and potentially alter metabolic risk. Funding Sources Supported by grant awards from the Department of Veteran's Affairs and the National Institute of Health.


2021 ◽  
Vol 22 (16) ◽  
pp. 8460
Author(s):  
Jose Cesar Rosa Neto ◽  
Philip C. Calder ◽  
Rui Curi ◽  
Philip Newsholme ◽  
Jaswinder K. Sethi ◽  
...  

Macrophages and lymphocytes demonstrate metabolic plasticity, which is dependent partly on their state of activation and partly on the availability of various energy yielding and biosynthetic substrates (fatty acids, glucose, and amino acids). These substrates are essential to fuel-based metabolic reprogramming that supports optimal immune function, including the inflammatory response. In this review, we will focus on metabolism in macrophages and lymphocytes and discuss the role of fatty acids in governing the phenotype, activation, and functional status of these important cells. We summarize the current understanding of the pathways of fatty acid metabolism and related mechanisms of action and also explore possible new perspectives in this exciting area of research.


2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.


2009 ◽  
Vol 4 (10) ◽  
pp. 1934578X0900401 ◽  
Author(s):  
Christel Brunschwig ◽  
François Xavier Collard ◽  
Jean-Pierre Bianchini ◽  
Phila Raharivelomanana

In order to establish a chemical fingerprint of vanilla diversity, thirty samples of V. planifolia J. W. Moore and V. tahitensis G. Jackson cured beans from seven producing countries were examined for their aroma and fatty acid contents. Both fatty acid and aroma compositions were found to vary between vanilla species and origins. Vanillin was found in higher amounts in V. planifolia (1.7-3.6% of dry matter) than in V. tahitensis (1.0-2.0%), and anisyl compounds were found in lower amounts in V. planifolia (0.05%) than in V. tahitensis (1.4%-2.1%). Ten common and long chain monounsaturated fatty acids (LCFA) were identified and were found to be characteristic of the vanilla origin. LCFA derived from secondary metabolites have discriminating compositions as they reach 5.9% and 15.8% of total fatty acids, respectively in V. tahitensis and V. planifolia. This study highlights the role of the curing method as vanilla cured beans of two different species cultivated in the same country were found to have quite similar fatty acid compositions.


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