Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects With Insulin Resistance

Abstract

Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity.

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

“…Our results document that 13-DHAHLA has the ability to affect immune cells, alleviate macrophage activation, and stimulate the proresolving processes. It is conceivable that DHAHLA may contribute to the anti-inflammatory and proresolving effects attributed to the DHA in human and murine WAT (lower density of crown-like structures, lower local concentration of proinflammatory cytokines), as was already documented for the other DHA metabolites, namely, docosanoids and related endocannabinoids (24)(25)(26)(27)(28)(29)(30)32). The expression of FAHFA hydrolases in WAT, liver, isolated adipocytes, and SVCs revealed that FAHFA degradation is probably regulated on both local and systemic levels.…”

“…Thus, in humans, in addition to their anti-inflammatory effects in WAT (see above), n-3 PUFAs attenuate systemic inflammatory processes (46), help to prevent cardiovascular disease (47), ameliorate nonalcoholic fatty liver disease (48), lower hypertriacylglycerolemia (49), and increase circulating adiponectin levels (50). Although n-3 PUFAs could not reverse type 2 diabetes and their impact on insulin sensitivity is controversial (23,28,34), n-3 PUFAs exert antiinflammatory effects in the WAT of human subjects with insulin resistance (28). As demonstrated by our clinical trial (34), which also served as a source of the samples for this study, n-3 PUFAs could improve postprandial lipid metabolism in overweight/obese patients with type 2 diabetes, even in the face of a combined pharmacotherapy.…”

“…This inflammatory response is accompanied by macrophage repolarization to the proinflammatory (classically activated) M1 state, which negatively affects WAT functions (20) and could be counteracted using both dietary and pharmacological interventions (21,22). Regarding the dietary influence, namely n-3 polyunsaturated FAs (PUFAs) of marine origin, which are considered to be healthy dietary constituents in individuals with diabetes (23) (see DISCUSSION), play an important role in the resolution of WAT inflammation (24)(25)(26)(27)(28) and probably potentiate beneficial functions of immune cells in WAT like efferocytosis or autophagy (17).…”

The Current Screening Technologies of Gene Expression Profile in Diabetes Mellitus

“…A study reported using NanoString nCounter system to characterize the gene expression in a patient within insulin resistant in respond to fish oil (omega-3) [38]. Other study had been reported using Illumina HiSeq 2005, Prabhakar, S.S. and colleagues to characterize the RNA expression of the kidney from diabetic rat [30].…”

Obesity, Inflammation and Neurological Alterations

“…Omega-3 polyunsaturated fatty acids ((0-3 PUFA) from fish oil have also antiinflammatory properties and therapeutic effects in inflammatory states including obesity (27). One of its actions is to inhibit the generation of MCP-l which has a potent chemotactic effect on both mast cells and macrophages (28) and regulate leukocyte trafficking to tissue sites of inflammation.…”