The effect of an increased free fatty acid concentration on thermogenesis and substrate oxidation in obese and lean men

Schiffelers, S.L.H.; Saris, W.H.M.; Baak, Marleen A. van

doi:10.1038/sj.ijo.0801528

Cited by 37 publications

(21 citation statements)

References 24 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that lipid oxidation and thermogenesis are impaired in the obese independently from NEFA availability. Our ␤ 1 -adrenoceptor study and the study using lipid heparin infusion (35) show that similar increases in thermogenesis and lipid oxidation occur in obese and lean men for a certain increase in plasma NEFA concentration, and therefore do not support these findings. The reduced increase in plasma NEFA and glycerol concentrations and the consequent reduced increases in lipid oxidation and thermogenesis during ␤ 2 -adrenergic stimulation might be explained not only by a defect in the ␤ 2 -adrenoceptor or the pathways it mediates, as stated above, but also by the slightly higher increase in insulin concentration in the obese, because insulin inhibits lipolysis.…”

Section: Discussioncontrasting

confidence: 53%

“…5, there was a clear relationship between the increases in plasma NEFA concentration and the increases in energy expenditure and lipid oxidation during ␤ 1 -and ␤ 2 -adrenergic stimulation. Furthermore, we recently reported that for a certain increase in plasma NEFA concentration produced by lipid heparin infusion, similar increases in thermogenesis and lipid oxidation are found in obese and lean men (35). These data suggest that not only ␤ 2 -adrenergic stimulation but also NEFA availability might be related to the blunted responses in thermogenesis and lipid oxidation.…”

Section: Discussionmentioning

confidence: 72%

See 1 more Smart Citation

1- and 2-Adrenoceptor-Mediated Thermogenesis and Lipid Utilization in Obese and Lean Men

Schiffelers¹

2001

Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

The aim of this study was to elucidate the roles of the ␤ 1 -and the ␤ 2 -adrenoceptors in thermogenesis and lipid utilization in obesity. The ␤ 1 -adrenoceptor study was performed in 9 obese and 10 lean men and consisted of 4 30-min periods during which subjects received consecutive infusions of 0, 3, 6, and 9 g/kg fat-free mass (FFM)⅐min dobutamine. Energy expenditure, lipid oxidation, and plasma nonesterified fatty acids and glycerol concentrations increased similarly in both groups during ␤ 1 -adrenergic stimulation. The ␤ 2 -adrenoceptor study was performed in 10 obese and 11 lean men and involved 3 45-min periods during which 0, 50, and 100 ng/kg FFM⅐min salbutamol were given in combination 1.2 g/kg FFM⅐min atenolol (bolus, 50 g/kg FFM). During ␤ 2 -adrenergic stimulation, the increases in energy expenditure and plasma nonesterified fatty acids and glycerol concentrations were reduced in the obese group. Furthermore, lipid oxidation significantly increased in the normal weight group, but remained similar in the overweight group. In conclusion, these data suggest that ␤ 1 -adrenoceptor-mediated metabolic processes are similar in both groups, but ␤ 2 -adrenoceptor-mediated increases in thermogenesis and lipid utilization are impaired in the obese. (J Clin Endocrinol Metab 86: [2191][2192][2193][2194][2195][2196][2197][2198][2199] 2001) T HE SYMPATHETIC nervous system plays an important role in the regulation of thermogenesis and lipid utilization. Studies in which the endogenous catecholamines norepinephrine (1, 2) and epinephrine (3-5) (both nonselective ␣-and ␤-adrenoceptor agonists) are infused show significant increases in energy expenditure, lipid oxidation, and lipolysis. The roles of the individual adrenoceptor subtypes in thermogenesis have also been studied. ␣-Adrenergic stimulation does not affect whole body thermogenesis (3, 6), whereas nonselective ␤-adrenergic stimulation with isoprenaline significantly increases energy expenditure and lipid utilization (7). During only ␤ 1 -adrenergic stimulation with dobutamine (8, 9) or only ␤ 2 -adrenergic stimulation with salbutamol (6) or terbutaline (10), energy expenditure, lipid oxidation, and lipolysis increase as well. In rats, ␤ 3 -adrenergic stimulation leads to significant increases in energy expenditure and lipid utilization (11,12). However, the rat ␤ 3 -adrenoceptor differs pharmacologically from the human ␤ 3 -adrenoceptor (13, 14), and consequently, the specific ␤ 3 -adrenoceptor agonists used in rats are only weak agonists in humans. Until now, no highly selective ␤ 3 -adrenoceptor agonist or antagonist has been available for administration in humans.Obese subjects may show an impaired response of thermogenesis during norepinephrine infusion (15, 16), but responses similar to those in lean subjects are also frequently found during norepinephrine (17, 18), epinephrine (5, 19), and isoprenaline (7) infusion. Others only found an impaired thermogenic response when very obese men were compared with very lean men (20) or only during ove...

show abstract

Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 72%

1- and 2-Adrenoceptor-Mediated Thermogenesis and Lipid Utilization in Obese and Lean Men

Schiffelers¹

2001

Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

“…Higher plasma FFA concentration may increase lipid oxidation and in turn the reliance on glucose as a source of energy (19). Additionally, plasma FFA may reduce insulin-stimulated glucose uptake (20).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Flexibility in Response to Glucose Is Not Impaired in People With Type 2 Diabetes After Controlling for Glucose Disposal Rate

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Compared with nondiabetic subjects, type 2 diabetic subjects are metabolically inflexible with impaired fasting fat oxidation and impaired carbohydrate oxidation during a hyperinsulinemic clamp. We hypothesized that impaired insulinstimulated glucose oxidation is a consequence of the lower cellular glucose uptake rate in type 2 diabetes. Therefore, we compared metabolic flexibility to glucose adjusted for glucose disposal rate in nondiabetic versus type 2 diabetic subjects and in the latter group after 1 year of lifestyle intervention (the Look AHEAD [Action For Health in Diabetes] trial).RESEARCH DESIGN AND METHODS-Macronutrient oxidation rates under fasting and hyperinsulinemic conditions (clamp at 80 mU/m 2 per min), body composition (dual-energy X-ray absorptiometry), and relevant hormonal/metabolic blood variables were assessed in 59 type 2 diabetic and 42 nondiabetic individuals matched for obesity, sex, and race. Measures were repeated in diabetic participants after weight loss.RESULTS-Metabolic flexibility to glucose (change in respiratory quotient [RQ]) was mainly related to insulin-stimulated glucose disposal rate (R 2 ϭ 0.46, P Ͻ 0.0001) with an additional 3% of variance accounted for by plasma free fatty acid concentration at the end of the clamp (P ϭ 0.03). The impaired metabolic flexibility to glucose observed in type 2 diabetic versus nondiabetic subjects (⌬RQ 0.06 Ϯ 0.01 vs. 0.10 Ϯ 0.01, respectively, P Ͻ 0.0001) was no longer observed after adjusting for glucose disposal rate (P ϭ 0.19). Additionally, the increase in metabolic flexibility to glucose after weight loss was accounted for by the concomitant increase in insulin-stimulated glucose disposal rate.CONCLUSIONS-This study suggests that metabolic inflexibility to glucose in type 2 diabetic subjects is mostly related to defective glucose transport. Diabetes 57:841-845, 2008 M etabolic flexibility is the capacity of the body to match fuel oxidation to fuel availability. It is typically assessed by the increase in respiratory quotient (RQ) from fasting to glucose/ insulin-stimulated conditions (1). During the overnight transition from the fed to the fasting state, metabolic inflexibility can also be evident by a higher fasting RQ (2). Finally, the lower capacity to adapt fat oxidation to a fat overload is another feature of metabolic inflexibility (3,4).Insulin-resistant and type 2 diabetic subjects have shown both higher fasting RQ (2,5,6) and blunted increase in RQ during a hyperinsulinemic clamp compared with insulin-sensitive subjects (2,7). Structural and functional mitochondrial impairments in obesity and type 2 diabetes are proposed to be a cause of insulin resistance and metabolic inflexibility (8,9).During a euglycemic-hyperinsulinemic clamp, the metabolic flexibility to glucose should be lower in type 2 diabetic versus nondiabetic subjects, since cellular glucose uptake rate and therefore free cellular glucose available for oxidation is reduced. Such phenomenon is analogous to the thermic effect of a meal, which is proporti...

show abstract

“…(11) and as adipocytes contain more lipids in obesity, the exosomes they secrete may be enriched in fatty acids, known positive regulators of FAO (25).…”

Section: Discussionmentioning

confidence: 99%

Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer

et al. 2016

View full text Add to dashboard Cite

Malignant progression results from a dynamic cross-talk between stromal and cancer cells. Recent evidence suggests that this cross-talk is mediated to a significant extent by exosomes, nanovesicles secreted by most cell types and which allow the transfer of proteins, lipids, and nucleic acids between cells. Adipocytes are a major component of several tumor microenvironments, including that of invasive melanoma, where cells have migrated to the adipocyte-rich hypodermic layer of the skin. We show that adipocytes secrete exosomes in abundance, which are then taken up by tumor cells, leading to increased migration and invasion. Using mass spectrometry, we analyzed the proteome of adipocyte exosomes. Interestingly, these vesicles carry proteins implicated in fatty acid oxidation (FAO), a feature highly specific to adipocyte exosomes. We further show that, in the presence of adipocyte exosomes, FAO is increased in melanoma cells. Inhibition of this metabolic pathway completely abrogates the exosome-mediated increase in migration. Moreover, in obese mice and humans, both the number of exosomes secreted by adipocytes as well as their effect on FAO-dependent cell migration are amplified. These observations might in part explain why obese melanoma patients have a poorer prognosis than their nonobese counterparts. Cancer Res; 76(14); 4051-7. Ó2016 AACR.

show abstract

The effect of an increased free fatty acid concentration on thermogenesis and substrate oxidation in obese and lean men

Cited by 37 publications

References 24 publications

1- and 2-Adrenoceptor-Mediated Thermogenesis and Lipid Utilization in Obese and Lean Men

1- and 2-Adrenoceptor-Mediated Thermogenesis and Lipid Utilization in Obese and Lean Men

Metabolic Flexibility in Response to Glucose Is Not Impaired in People With Type 2 Diabetes After Controlling for Glucose Disposal Rate

Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer

Contact Info

Product

Resources

About