Arachidonic acid/docosahexaenoic acid‐supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3Leiden mice

Abstract

Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and mild obesity. Methods and results: Four-week-old male ApoE*3Leiden mice were fed chow diet with or without a mixture of ARA (0.129 wt%) and DHA (0.088 wt%) or Omacor (0.30 wt% EPA, 0.25 wt% DHA). At age 12 weeks, mice were fed high-fat/high-carbohydrate (HFHC) diet without above supplements until age 20 weeks. Control mice received chow diet throughout the study. Mice receiving ARA/DHA gained less body weight compared to control and this effect was sustained when fed HFHC. Omacor had no significant effect on body weight gain. Plasma cholesterol and triglycerides were significantly lowered by both supplementations. At 20 weeks, epididymal fat mass was less in ARA/DHA-supplemented mice, while Omacor had no significant effect on fat mass. Both ARA/DHA and Omacor reduced inguinal adipocyte cell size; only ARA/DHA significantly reduced epididymal macrophage infiltration. Conclusion: This study shows that early life ARA/DHA, but not Omacor supplementation improves body weight gain later in life. ARA/DHA and to a lesser extent Omacor both improved adipose tissue quality.

Coordinated and Interactive Expression of Genes of Lipid Metabolism and Inflammation in Adipose Tissue and Liver during Metabolic Overload

“…Non-alcoholic fatty liver disease was analyzed as described [21] and vacuolization (micro- and macrovaculolization) and hepatocellular hypertrophy were scored. Sections of epididymal adipose tissue were prepared following a similar procedure [22] and stained with HPS for computer-assisted morphological assessment of adipocyte size and analysis of macrophage accumulation in crown-like structures essentially as reported [20]. CCR2 positive cells were detected using antibody (Abcam ab21667, Cambridge, UK).…”

“…APOE*3Leiden mice have a humanized lipoprotein metabolism and develop obesity, insulin resistance and NAFLD during HFD feeding [18-20]. Bayesian cluster analysis in conjunction with promoter analysis and biochemical measurements showed that adjustment of lipid metabolism and onset of inflammation in WAT occurs sequentially and is orchestrated by specific master regulators that also control comparable changes in lipid metabolism and inflammation in the liver later in time.…”

A casein hydrolysate based formulation attenuates obesity and associated non-alcoholic fatty liver disease and atherosclerosis in LDLr-/-.Leiden mice

“…However, most of these studies investigated the effects of the n-3 LC-PUFA DHA [19–21], whereas supplementation with n-6/n-3 LC-PUFAs at a particular ratio (2:1) has been associated with health effects in humans and animal studies. [14, 15, 22, 23] We therefore tested a well-defined n-6/n-3 LCPUFA mixture of ARA/DHA as present in breast milk. In addition to eHC and LC-PUFAs, we also employed a well characterized probiotic LGG that has been shown to affect inflammatory responses in children [24] and that may ameliorate experimental NAFLD.…”

Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

“…Similar to the liver, intrarenal accumulation of lipids has been proposed to play a major role in causing diabetes associated nephropathy [10]. For example, intrarenal lipid accumulation induces glomerular expression of MCP-1 and VCAM-1 [15], [16], which contribute to glomerular macrophage accumulation [8], [17], eventually leading to albuminuria [18].…”

“…To address this question, the current study was designed to test whether an alternating diet strategy would also be beneficial for fat- containing diets wherein high fat diet is alternated with low fat diet. Previously, it has been shown that feeding E3L male mice on a western type high- fat diet leads to insulin resistance and inflammation in both liver and adipose tissue [9], [10]. In the current study, we investigated whether an alternating low- fat (4 days)/high- fat (3 days) dietary regimen was able to diminish the adverse effects caused by a continuous high- fat diet in E3L mice.…”