A Distinct Fatty Acid Profile Underlies the Reduced Inflammatory State of Metabolically Healthy Obese Individuals

Perreault, Maude; Zulyniak, Michael A.; Badoud, Flavia; Stephenson, Susan; Badawi, Alaa; Buchholz, Annick; Mutch, David M.

doi:10.1371/journal.pone.0088539

Cited by 59 publications

(86 citation statements)

References 49 publications

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“…These studies have consistently shown elevated levels of C14:0 (myristic acid) in adults as well [13,32,33]. A study on lean, healthy, metabolically healthy, and metabolically unhealthy obese adults showed that C14:0 even has a dose-response relationship with the status of obesity and according to the degree of obesity-related inflammation [33]. Whether this would show up also in children with different degrees of obesity or explicitly for LPCaC14:0 is an open question.…”

Section: Discussionmentioning

confidence: 98%

Rapid Growth and Childhood Obesity Are Strongly Associated with LysoPC(14:0)

Rzehak

Hellmuth²,

Uhl³

et al. 2014

Ann Nutr Metab

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Background: Despite the growing interest in the early-origins-of-later-disease hypothesis, little is known about the metabolic underpinnings linking infant weight gain and childhood obesity. Objective: To discover biomarkers reflective of weight change in the first 6 months and overweight/obesity at age 6 years via a targeted metabolomics approach. Design: This analysis comprised 726 infants from a European multicenter randomized trial (Childhood Obesity Programme, CHOP) for whom plasma blood samples at age 6 months and anthropometric data up to the age of 6 years were available. ‘Rapid growth' was defined as a positive difference in weight within the first 6 months of life standardized to WHO growth standards. Weight change was regressed on each of 168 metabolites (acylcarnitines, lysophosphatidylcholines, sphingomyelins, and amino acids). Metabolites significant after Bonferroni's correction were tested as predictors of later overweight/obesity. Results: Among the overall 19 significant metabolites, 4 were associated with rapid growth and 15 were associated with a less-than-ideal weight change. After adjusting for feeding group, only the lysophosphatidylcholine LPCaC14:0 remained significantly associated with rapid weight gain (β = 0.18). Only LPCaC14:0 at age 6 months was predictive of overweight/obesity at age 6 years (OR 1.33; 95% CI 1.04-1.69). Conclusion: LPCa14:0 is strongly related to rapid growth in infancy and childhood overweight/obesity. This suggests that LPCaC14:0 levels may represent a metabolically programmed effect of infant weight gain on the later obesity risk. However, these results require confirmation by independent cohorts.

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Section: Discussionmentioning

confidence: 98%

Rapid Growth and Childhood Obesity Are Strongly Associated with LysoPC(14:0)

Rzehak

Hellmuth²,

Uhl³

et al. 2014

Ann Nutr Metab

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“…The importance of unsaturated fatty acids in mediating inflammation is enhanced by a recent study showing a distinct fatty acid profile between MHO and unhealthy obese individuals, specifically for saturated fatty acids [64]. Further comparisons of these two groups are required to better identify potential mechanisms of protection against obesity-related insulin resistance and inflammation and to develop preventive and therapeutic strategies.…”

Section: Page 11 Of 24mentioning

confidence: 99%

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Esser

Legrand-Poels

Piette

et al. 2014

Diabetes Research and Clinical Practice

1,625

1,064

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:It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes.

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“…Taken together, these findings suggest that a fat-enriched diet is central to the loss of epithelial barrier integrity, which in turn directly or indirectly affects the microbiota, causing a dysbiosis that further alters epithelial homeostasis. Several studies have addressed the long-term effects of HF diet in such pathologies (40)(41)(42). Interestingly, most studies have characterized the fecal or cecal luminal microbiota; however, very few have attempted to characterize the mucosa-associated microbiota in the upper digestive segments, even though basic functions performed by the SI need to be tightly preserved to maintain health.…”

Section: Significancementioning

confidence: 99%

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

Tomas

Mulet

Saffarian

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

203

146

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Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum—which is usually described as free of bacteria—became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus. A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ–deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

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A Distinct Fatty Acid Profile Underlies the Reduced Inflammatory State of Metabolically Healthy Obese Individuals

Cited by 59 publications

References 49 publications

Rapid Growth and Childhood Obesity Are Strongly Associated with LysoPC(14:0)

Rapid Growth and Childhood Obesity Are Strongly Associated with LysoPC(14:0)

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

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