scholarly journals Increased adiposity by feeding growing rats a high-fat diet results in iron decompartmentalisation

2019 ◽  
Vol 123 (10) ◽  
pp. 1094-1108
Author(s):  
Alexandre R. Lobo ◽  
Eduardo H. S. Gaievski ◽  
Carlos Henrique de Mesquita ◽  
Eduardo De Carli ◽  
Pryscila Dryelle S. Teixeira ◽  
...  
Keyword(s):  
Atomic Absorption Spectrophotometry ◽  
Whole Body ◽  
Radiological Protection ◽  
Mrna Levels ◽  
High Fat ◽  
Protein Levels ◽  
Growing Rats ◽  
Biokinetic Model ◽  
Body Adiposity ◽  
Ferroportin 1

AbstractThe present study reports the effects of a high-fat (HF) diet of over 8 weeks on the Fe status of growing rats. Tissue Fe levels were analysed by atomic absorption spectrophotometry, and whole-body adiposity was measured by dual-energy X-ray absorptiometry. Histopathology and morphometry of adipose tissue were performed. Liver homogenates were used for measuring ferroportin-1 protein levels by immunoblotting, and transcript levels were used for Fe genes measured by real-time PCR. Tissue Fe pools were fit to a compartmental biokinetic model in which Fe was assessed using fourteen compartments and twenty-seven transfer constants (kj,i from tissue ‘i’ to tissue ‘j’) adapted from the International Commission on Radiological Protection (ICRP) 69. Ten kj,i were calculated from the experimental data using non-linear regression, and seventeen were estimated by allometry according to the formula ${k_{i,j}} = a \times {M^b}$. Validation of the model was carried out by comparing predicted and analysed Fe pool sizes in erythrocytes, the liver and the spleen. Body adiposity was negatively associated with serum Fe levels and positively associated with liver Fe stores. An inferred increase in Fe transfer from bone marrow to the liver paralleled higher hepatic Fe concentrations and ferritin heavy-chain mRNA levels in the HF diet-fed animals, suggesting that liver Fe accumulation occurred at least in part due to a favoured liver erythrocyte uptake. If this feeding condition was to be prolonged, impaired Fe decompartmentalisation may occur, ultimately resulting in dysmetabolic Fe overload.

scholarly journals Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark

Diabetologia ◽  
2021 ◽  
Author(s):  
Juliana de Almeida-Faria ◽  
Daniella E. Duque-Guimarães ◽  
Thomas P. Ong ◽  
Lucas C. Pantaleão ◽  
Asha A. Carpenter ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Maternal Obesity ◽  
Luciferase Assay ◽  
Whole Body ◽  
Mrna Levels ◽  
Protein Levels ◽  
Novel Targets

Abstract Aims/hypothesis Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. Methods miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic–hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. Results The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. Conclusions/interpretation Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target. Graphical abstract

scholarly journals Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast

2016 ◽  
Vol 311 (1) ◽  
pp. E224-E235 ◽  
Author(s):  
Ann Mosegaard Bak ◽  
Andreas Buch Møller ◽  
Mikkel Holm Vendelbo ◽  
Thomas Svava Nielsen ◽  
Rikke Viggers ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fat Mass ◽  
Muscle Protein ◽  
Whole Body ◽  
Mrna Levels ◽  
Mass Unit ◽  
Body Protein ◽  
Protein Levels ◽  
Tracer Techniques ◽  
Obese Subjects

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein.

Different contribution of muscle and liver lipid metabolism to endurance capacity and obesity susceptibility of mice

2009 ◽  
Vol 106 (3) ◽  
pp. 871-879 ◽  
Author(s):  
Satoshi Haramizu ◽  
Azumi Nagasawa ◽  
Noriyasu Ota ◽  
Tadashi Hase ◽  
Ichiro Tokimitsu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Lipid ◽  
Whole Body ◽  
Endurance Capacity ◽  
High Fat ◽  
Oxidation Activity ◽  
Protein Levels ◽  
Liver Lipid Metabolism ◽  
Obesity Susceptibility ◽  
Body Energy

We investigated strain differences in whole body energy metabolism, peripheral lipid metabolism, and energy metabolism-related gene expression and protein levels in BALB/c, C57BL/6J, and A/J mice to evaluate the relationship between endurance capacity, susceptibility to diet-induced obesity, and differences in lipid metabolism in muscle and liver. A high-fat diet significantly increased body weight and fat weight in C57BL/6J mice, but not in BALB/c and A/J mice. The endurance capacity of BALB/c mice was 52% greater than that of C57BL/6J mice and 217% greater than that of A/J mice. The respiratory exchange ratio was lowest in BALB/c mice, higher in C57BL/6J mice, and highest in A/J mice, which inversely correlated with the endurance capacity and fatty acid β-oxidation activity in the muscle. Plasma lactate levels measured immediately after exercise were lowest in BALB/c mice and highest in A/J mice, although there was no difference under resting conditions, suggesting that carbohydrate breakdown is suppressed by enhanced fat utilization during exercise in BALB/c mice. On the other hand, the body weight increase induced by high-fat feeding was related to a reduced whole body energy expenditure, higher respiratory quotient, and lower fatty acid β-oxidation activity in the liver. In addition, β-oxidation activity in the muscle and liver roughly paralleled the mRNA and protein levels of lipid metabolism-related molecules, such as peroxisome proliferator-activated receptor and medium-chain acyl-CoA dehydrogenase, in each tissue. These findings indicate that genetically determined basal muscle and liver lipid metabolism and responsiveness to exercise influence physical performance and obesity susceptibility.

scholarly journals A comparative study on the effects of high-fat diet and endurance training on the PGC-1α-FNDC5/irisin pathway in obese and nonobese male C57BL/6 mice

2018 ◽  
Vol 43 (7) ◽  
pp. 651-662 ◽  
Author(s):  
Fatemeh Kazeminasab ◽  
Sayed Mohammad Marandi ◽  
Kamran Ghaedi ◽  
Zahra Safaeinejad ◽  
Fahimeh Esfarjani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Messenger Rna ◽  
Muscle Protein ◽  
Exercise Session ◽  
Mrna Levels ◽  
Skeletal Muscle Protein ◽  
High Fat ◽  
Low Fat ◽  
Protein Levels

The present study was performed to clarify how a combined exercise/diet treatment could affect the expression level of the muscle fibronectin type III domain containing 5 (Fndc5) with respect to body fat mass. Male C57BL/6 mice were divided into 2 groups including low-fat (LF) and high-fat (HF) diets for 12 weeks. Then, LF fed (nonobese) and HF fed mice (obese) were divided into the following 4 groups: HF-Exercise, HF-Sedentary, LF-Exercise, and LF-Sedentary. The exercise group exercised on a motor-driven treadmill for 45 min/day, 5 days/week for 8 weeks. Mice were sacrificed 24 h after the final exercise session. Gastrocnemius muscle and the visceral adipose tissue were excised and frozen for the assessment of proliferator-activated receptor gamma coactivator 1 alpha (Pgc-1α) and Fndc5 messenger RNA (mRNA) and protein levels. Data indicated that protein level of muscle PGC-1α was decreased in HF versus LF groups and in obese versus nonobese mice. Moreover, Fndc5 mRNA levels were increased in the muscle tissue of HF versus LF groups and in obese versus nonobese mice. Also, in the gastrocnemius skeletal muscle, protein levels of FNDC5 were significantly higher in the HF fed mice, as compared with their low-fat fed counterparts, similar to what was observed for exercised versus sedentary mice. Overall, we found that the HF diet increased Fndc5 transcript levels in the skeletal muscle, but exercise had a minimal effect on the transcript level of Fndc5, whereas endurance training increased the protein content of FNDC5 in the skeletal muscle.

Abstract 693: TLR3 Modulates Inflammation and Lipolysis in Visceral Adipose Tissue in High Fat Diet-fed Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Cuiqing Liu ◽  
Guohua Lin ◽  
Guoqing Zhang ◽  
Huanhuan Wang ◽  
Hongping Yin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Fat Diet ◽  
Dietary Factors ◽  
Whole Body ◽  
Mrna Levels ◽  
High Fat ◽  
M1 Macrophage ◽  
Visceral Adipose ◽  
Fat Feeding

Inflammation in insulin sensitive tissues, the visceral adipose tissue (VAT), is a central abnormality in obesity/insulin resistance (IR), with recruitment of innate immune cells such as monocytes into adipose tissue driving the development of glucose and lipoprotein dysregulation. We evaluated the role of Toll like receptor 3 (TLR3) in high fat diet-induced obesity and IR. Wild-type C57BL/6 and TLR3 -/- male mice were fed a high fat diet for 15 weeks. High fat feeding resulted in increased TLR3 expression in VAT. TLR3 deficiency attenuated the high fat diet-increased body weight, fasting blood glucose, whole body IR and impaired glucose tolerance. Morphologically, high fat diet induced adiposity and enlarged adipocyte area in VAT, which were attenuated in TLR3 -/- mice. Functionally, high fat diet induced dysregulation of adipocytokines such as downregulation of adiponectin and resistin, upregulation of leptin in VAT, with the disturbance of adiponectin and leptin was corrected in TLR3-/- mice. In addition, high fat diet inhibited insulin pathway, accompanied with decreased phosphorylation of AMPK and lowered expression of lipolysis-related enzymes such as HSL and ATGL, both at the mRNA levels and protein levels, all of which was corrected by TLR3 deficiency. Finally, TLR3 deletion suppressed the high fat feeding-mediated macrophage polarization, evidenced by increased type M1 macrophage (F4/80+/CD11c+/CD206-) infiltration and upregulation of M1 genes such as IL-6 and TNFα. TLR3 modulates high fat diet-induced IR and obesity by suppressing M1 macrophage-mediated VAT inflammation, facilitating secretion of adipocyte-derived hormones, thus enhanced AMPK activity and adipose lipolysis. These findings provide new mechanistic links between dietary factors-mediated IR and associated abnormalities in lipid metabolism and adipose inflammation.

scholarly journals Hypothalamic alterations in fetuses of high fat diet-fed obese female rats

2008 ◽  
Vol 200 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Anshu Gupta ◽  
Malathi Srinivasan ◽  
Supaporn Thamadilok ◽  
Mulchand S Patel
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Maternal Obesity ◽  
Late Gestation ◽  
Female Rats ◽  
Melanocortin Receptor ◽  
Mrna Levels ◽  
High Fat ◽  
Control Female ◽  
Protein Levels

The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats; additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation compared with control female rats that were fed a standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups. FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor β-subunit. However, the protein levels of signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agouti-related polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides and leptin and insulin signaling in the late fetal period.

scholarly journals HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

2009 ◽  
Vol 296 (2) ◽  
pp. E291-E299 ◽  
Author(s):  
Christy L. White ◽  
Amy Whittington ◽  
Maria J. Barnes ◽  
Zhong Wang ◽  
George A. Bray ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Leptin Resistance ◽  
Whole Body ◽  
Mrna Levels ◽  
Protein Levels ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Concomitant Reduction ◽  
Specific Deletion

Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus ( P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA levels was also observed in rats chronically infused with leptin (3 μg/day icv) for 14 days ( P = 0.01) and in leptin-deficient ob/ ob mice infused with leptin (5 μg/day sc for 14 days; P = 0.003). When saline-infused ob/ ob mice were placed on a HF diet for 14 days, an increase in hypothalamic PTP1B mRNA expression was detected ( P = 0.001) despite the absence of circulating leptin. In addition, although ob/ ob mice were much more sensitive to leptin on a low-fat (LF) diet, a reduction in this sensitivity was still observed following exposure to a HF diet. Taken together, these data indicate that hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance. However, these data also indicate that leptin is not required for the increase in hypothalamic PTP1B or the development of leptin resistance. Therefore, additional, leptin-independent mechanisms must exist that increase hypothalamic PTP1B and contribute to leptin resistance.

scholarly journals Hepatic F-box Only Protein 2 (FBXO2) Might Not Mediate Glucose Homeostasis in Obese Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1281-1281
Author(s):  
Siau Yen Wong ◽  
Peiran Lu ◽  
Lei Wu ◽  
Mckale Montgomery ◽  
Winyoo Chowanadisai ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Fasting Blood Glucose ◽  
Whole Body ◽  
Diabetic Mice ◽  
High Fat ◽  
Diet Intervention ◽  
Protein Levels ◽  
Mitochondrial Superoxide ◽  
Primary Mouse

Abstract Objectives F-box only protein 2 (FBXO2) is an E3 ubiquitin protein ligase highly expressed in the brain and cochlea, hepatic FBXO2 protein levels are very low in healthy mice. It was reported that hepatic FBXO2 elevation causes hyperglycemia in obese mice. Here, we investigated whether hepatic FBXO2 expression was enhanced in diabetic human samples; and if so, whether deficiency of FBXO2 could improve blood glucose control in diet-induced obese diabetic mice. Methods Human liver specimen samples from healthy and type 2 diabetic human subjects were subject to transcriptomics and proteomics. The results were confirmed by real-time QPCR and immunoblotting, respectively. Male FBXO2 whole-body knockout (KO) and C57BL/6 J mice (WT, genetic background) at 6 weeks of age were fed a high fat (26% kCal)/high sucrose (15% kCal)/high fructose (15% kCal) diet for 8 weeks. Food intake and body weight gain were monitored weekly. Glucose tolerance and insulin tolerance tests were performed at the 7th week of dietary intervention. At the termination of intervention, mice were euthanized, and blood and liver tissues were collected for further assessment. Primary mouse embryonic fibroblasts (MEF) cells were isolated from WT and KO mice. Mitochondrial superoxide was detected by MitoSOX live cell staining. Results Transcriptomics and proteomics results showed vast shifts in pathways involved in energy metabolism and mitochondrial function, and significant elevation of FBXO2 expression at mRNA and protein levels in diabetic human livers. However, deficiency of FBXO2 did not alter mitochondrial superoxide production in MEF cells and did not cause an elevation of the fasting blood glucose level before a diet feeding. Moreover, both strains had significantly elevated fasting blood glucose levels after the high-fat diet intervention but did not differ by strains. The insulin sensitivity had no significant difference between strains after diet intervention. Conclusions The results suggested that FBXO2 depletion did not alter glucose homeostasis in diet-induced obese mouse models, though diabetic humans had a highly elevated hepatic FBXO2 level. Funding Sources N/A.

scholarly journals A259 HIGH-FAT/HIGH-CHOLESTEROL DIETS PREDISPOSE THE HOST TO EXACERBATED ENTERIC INFECTIONS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 136-137
Author(s):  
J Valdes ◽  
A Armas ◽  
J Gagné Sansfaçon ◽  
V Reyes-Nicolas ◽  
N Rivard ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Molecular Mechanisms ◽  
Goblet Cells ◽  
Sodium Cholate ◽  
Whole Body ◽  
Mrna Levels ◽  
Mucus Layer ◽  
High Cholesterol ◽  
High Fat ◽  
Enteric Infections

Abstract Background High-fat/high-cholesterol diets are a well established risk factor for cardiovascular and metabolic diseases, given their propensity to trigger perturbations ranging from altering whole body lipid profile to the induction of intestinal dysbiosis. However much less is known about their effects on the host’s susceptibility to enteric infections. Aims To determine the effects of high-fat/high-cholesterol diets over the host’s susceptibility to enteric bacterial infections and identify the underlying molecular mechanisms. Methods C57BL/6 mice were given two different high-fat/high-cholesterol diets; HFHC (40% kcal fat, 1.25% cholesterol) or HFHCC (40% kcal fat, 1.25% cholesterol, 0.5% sodium cholate) and a control, normal diet (ND, 10% kcal fat, 0% cholesterol, 0% sodium cholate). After four weeks of administration, animals were euthanized and colonic tissue samples taken for histology, immunofluorescence, gene expression analyses, total protein lysates and microbiome sequencing (16S). A separated group of animals was gavaged with FITC-dextran to measure intestinal permeability. Mice fed with the diets for three weeks were infected with ~5x108 cfu of Citrobacter rodentium DBS100/StrpR by oral gavage, and kept on the corresponding diets after the infections. Bacterial shedding in the feces was followed for up to 30 days after infection. Results Administration of the HFHC and HFHCC diets caused an increase in intestinal permeability. Colonic sections stained with H&E and alcian blue evidenced a decreased in the number of mucin-filled goblet cells and a thinner mucus layer, suggesting a defect in the assembly and/or stability of the mucus layer. Expression analyses revealed a drop in the mRNA levels of Muc1 and Muc2, suggesting reduced mucin production. The concentration of IgA was slightly reduced in colon lysates and the transcript levels of the antimicrobial peptide genes Ang4, Leap2 and Cramp were also significantly reduced. Immunofluorescent microscopy showed that goblet cell granules of HFHC- and HFHCC-fed mice were devoid of Relmβ and Tff3, indicating defective production of those two factors critical for intestinal epithelial defense and homeostasis. Collectively, our results suggest that HFHC and HFHCC diets induce differentiation and functional defects in goblet cells. Fecal shedding of C. rodentium showed an increased bacterial burden in HFHC- and HFHCC-fed animals, indicating a more aggressive bacterial infection, accompanied by increased epithelial damage. Conclusions Consumption of high-fat/high cholesterol diets perturb the colonic homeostasis and alter intestinal defenses and the integrity of the intestinal barrier, predisposing the host to a higher susceptibility to enteric infections. Funding Agencies CIHRNSERC

scholarly journals FFAR4 (GPR120) Signaling Is Not Required for Anti-Inflammatory and Insulin-Sensitizing Effects of Omega-3 Fatty Acids

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Simone Isling Pærregaard ◽  
Marianne Agerholm ◽  
Annette Karen Serup ◽  
Tao Ma ◽  
Bente Kiens ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Whole Body ◽  
Low Grade ◽  
Omega 3 ◽  
High Fat ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
High Sucrose

Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects ofω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects ofω3-PUFAs remain to be elucidated. In the present study, we usedFfar4knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucroseω3-PUFA; or high fat, high sucroseω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fedω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover,ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated byω3-PUFAs.

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