The effect of quantity and quality of dietary fat intake on subcutaneous white adipose tissue inflammatory responses

Abstract

The global prevalence of obesity and obesity-associated cardiometabolic diseases is a significant public health burden. Chronic low-grade inflammation in metabolic tissues such as white adipose tissue (WAT) is linked to obesity and may play a role in disease progression. The overconsumption of dietary fat has been suggested to modulate the WAT inflammatory environment. It is also recognised that fats varying in degree of fatty acid saturation may elicit differential WAT inflammatory responses. This information has originated predominantly from animal or cell models and translation into human participants in vivo remains limited. This review will summarise human intervention studies investigating the effect of dietary fat quantity and quality on subcutaneous WAT inflammation, with a specific focus on the toll-like receptor 4 (TLR4)/NF-κB and nucleotide-binding and oligomerisation domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome molecular signalling pathways. Overall, firm conclusions are hard to draw regarding the effect of dietary fat quantity and quality on WAT inflammatory responses due to the heterogeneity of study designs, diet composition and participant cohorts recruited. Previous studies have predominantly focused on measures of WAT gene expression. It is suggested that future work includes measures of WAT total content and phosphorylation of proteins involved in TLR4/NF-κB and NLRP3 signalling as this is more representative of alterations in WAT physiological function. Understanding pathways linking the intake of total fat and specific fatty acids with WAT metabolic-inflammatory responses may have important implications for public health by informing dietary guidelines aimed at cardiometabolic risk reduction.

Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial

“…28,29 Furthermore, EPA and DHA can bind to receptors such as peroxisome proliferator activated receptors (PPARs) 30 to regulate the expression of genes associated with lipid accumulation in WAT, 31,32 and to G-protein coupled receptor (GPR)-120 to regulate inflammation and insulin sensitivity. 33 Therefore, EPA and DHA have the potential to reduce inflammation in adipose tissue but investigation of this in human scWAT is limited, as highlighted in a recent review by Dewhurst-Trigg et al 34 Obesity is accompanied by several pathophysiological changes in adipose tissue, but the mechanisms behind these have not been well elucidated with reports predominantly focussing on circulating markers of inflammation. In addition, the metabolic health of individuals living with obesity is often overlooked when trying to understand the link between obesity and adipose tissue inflammation which can also be said for assessing the effects of LC n-3 PUFAs.…”

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

“…During the feeding/fasting cycle, in physiological conditions, an intermittent, non-specific, low-grade inflammatory response occurs at the level of “metabolic tissues” (adipose, muscle, and liver tissue), which results in a transient increase in some inflammatory proteins/cytokines in the serum. This increment reaches its maximum peak during the absorption phase (post-prandial) and then gradually decreases in about 2 h, when the nutrients have been distributed, metabolized, and/or accumulated in the respective cellular sites [ 32 ]. The inflammatory response is amplified in overeating conditions (hyperlipidic diet, excess of saturated fats and simple carbohydrates, and low intake of fiber, vitamins, and antioxidant compounds), in obesity, and in diabetes—when the metabolic overload generates a “traffic jam” of the physiological metabolic pathways, progressive recruitment and activation of immune-competent cells, such as macrophages, mast cells, and T lymphocytes, occurs [ 33 ].…”

“…An examination of data from the National Health and Nutrition Examination Survey (NHANES 99-00) found that levels of SFAs in serum phospholipids of male civil servant workers (40–69 years) positively correlated with some inflammatory markers, such as HS-CRP (high sensitivity C-reactive protein) and fibrinogen; by contrast, phospholipid PUFA levels were inversely associated with HS-CRP [ 32 , 36 ]. It has been recently shown in a C57BL/6 male mice model that consuming a high-fat diet, enriched with SFAs, induces especially adipose IL-1β inflammation and insulin resistance.…”

“…In conclusion, SFAs impair insulin signaling through TLR4, activating the NF-κB pathway and NLRP3 inflammasome that promotes the conversion of pro-IL-1β into mature IL-1β [ 16 , 31 , 32 ]. In a clinical study, the relationship between SFAs and inflammation biomarkers has been demonstrated in subjects with excess weight, in which the ω6:ω3 ratio is directly related to the concentrations of IL-6, CRP, and adhesion molecules; in addition, the inhibition of IRS-1 and the reduction in adiponectin levels induce IR, thus increasing the risk of the metabolic syndrome [ 21 ].…”

Short-term High-fat Overfeeding Does Not Induce NF-κB Inflammatory Signaling in Subcutaneous White Adipose Tissue

“…We also recently reported that a 7-day period of lipid oversupply plays a role in the development of vascular inflammation and atherosclerosis (8). However, there is very little information on the initiation of inflammatory signaling pathways within WAT in response to acute overnutrition (9). Previous high-fat overfeeding studies (3-to 56-days) have examined gene expression of targets involved in WAT inflammatory pathways, such as pro-inflammatory cytokines (IL-6, TNF-α and MCP-1), macrophage markers (cluster of differentiation (CD)68, CD11c and CD40), and components of the NF-κB pathway (10)(11)(12)(13)(14).…”