Plasma Free Fatty Acid Turnover Rate in Obesity

Björntorp, Per; Bergman, Halvar; Varnauskas, E

doi:10.1111/j.0954-6820.1969.tb07347.x

Cited by 142 publications

(67 citation statements)

References 23 publications

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“…We show that exposure to sera from obese postmenopausal women stimulates significantly greater macrophage COX-2 expression and a 5-fold increase in PGE2 production. Saturated fatty acids can promote COX-2 expression and PGE2 production in cultured macrophages (15,31), and the increased lipolysis that accompanies obesity results in a higher concentration of circulating free fatty acids, particularly palmitate (32)(33)(34). We confirmed that the obese patient sera contains significantly higher levels of palmitate, total saturated fatty acids, and arachidonic acid, the omega-6 fatty acid substrate utilized by COX-2 to produce PGE2.…”

Section: Discussionsupporting

confidence: 64%

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

et al. 2014

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Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor a (ERa)-positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERa-positive patients with an average body mass index of >30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERa activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted. Cancer Res; 74(16); 4446-57. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 64%

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

et al. 2014

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“…Although muscle tissue is not thought to significantly contribute to overall lipid production, ectopic lipid accumulation is associated with IR and NEFA in tissues, including muscle, and is thought to cause lipotoxicity and promote IR. Although increased fatty acid levels may indicate a larger supply from plasma by enhanced adipose tissue lipolysis or decreased fatty acid clearance [20,21], increased activity of muscle-specific fatty acid synthase (FAS) might also contribute to increased levels of fatty acids [22].…”

Section: Discussionmentioning

confidence: 99%

Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes

et al. 2015

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Aims/hypothesis Metabolomics approaches in humans have identified around 40 plasma metabolites associated with insulin resistance (IR) and type 2 diabetes, which often coincide with those for obesity. We aimed to separate diabetesassociated from obesity-associated metabolite alterations in plasma and study the impact of metabolically important tissues on plasma metabolite concentrations. Methods Two obese mouse models were studied; one exclusively with obesity (ob/ob) and another with type 2 diabetes (db/db). Both models have impaired leptin signalling as a cause for obesity, but the different genetic backgrounds determine the susceptibility to diabetes. In these mice, we profiled plasma, liver, skeletal muscle and adipose tissue via semiquantitative GC-MS and quantitative liquid chromatography (LC)-MS/MS for a wide range of metabolites. Results Metabolite profiling identified 24 metabolites specifically associated with diabetes but not with obesity. Among these are known markers such as 1,5-anhydro-D-sorbitol, 3-hydroxybutyrate and the recently reported marker glyoxylate. New metabolites in the diabetic model were lysine, Ophosphotyrosine and branched-chain fatty acids. We also identified 33 metabolites that were similarly altered in both models, represented by branched-chain amino acids (BCAA) as well as glycine, serine, trans-4-hydroxyproline, and various lipid species and derivatives. Correlation analyses showed stronger associations for plasma amino acids with adipose tissue metabolites in db/db mice compared with ob/ob mice, suggesting a prominent contribution of adipose tissue to changes in plasma in a diabetic state. Conclusions/interpretation By studying mice with metabolite signatures that resemble obesity and diabetes in humans, we have found new metabolite entities for validation in appropriate human cohorts and revealed their possible tissue of origin.

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“…compartmental model; glucose tolerance test PLASMA nonesterified fatty acids (NEFAs) are important substrates for triglyceride synthesis and gluconeogenesis, and they provide fuel for oxidation in nonadipose tissue (9, 14). Elevated plasma concentrations of NEFA are involved in the development of hypertriglyceridemia and insulin resistance as are often seen in pathological conditions, such as diabetes mellitus, obesity, hypertension, and coronary heart disease (6,7,8,22,25,32,35).…”

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confidence: 99%

A novel minimal model to describe NEFA kinetics following an intravenous glucose challenge

Boston

Moate²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Dynamics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification if we are to understand the etiology of such diseases as type 1 and 2 diabetes, as well as metabolic syndrome and obesity, or if we are to elucidate the mechanism of action of various interventions. We present a new compartmental model that employs the pattern of plasma glucose concentrations in healthy young adults to predict dynamic changes that occur in plasma NEFA concentrations during either a glucose-only intravenous glucose tolerance test, or an insulin-modified intravenous tolerance test, or a modified protocol during which variable-rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dl. The model described all of the major features of NEFA response to an intravenous glucose tolerance test, including an initial latency phase, a phase during which plasma NEFA concentrations plummet to a nadir, and a rebound phase during which plasma NEFA concentrations may rise to a plateau concentration, which may be substantially higher than the initial basal NEFA concentration. This model is consistent with physiological processes and provides seven adjustable parameters that can be used to quantify NEFA production (lipolysis) and utilization (oxidation). When tested on data from the scientific literature, the range in estimated rate of lipolysis was 24-36 micromol.l(-1).min(-1) and for NEFA oxidation rate was 25-54 micromol.l(-1).min(-1). All model parameters were well identified and had coefficients of variation < 15% of their estimated values. It is concluded that this model is suitable to describe NEFA kinetics in human subjects.

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Plasma Free Fatty Acid Turnover Rate in Obesity

Cited by 142 publications

References 23 publications

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes

A novel minimal model to describe NEFA kinetics following an intravenous glucose challenge

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