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Abstract Objective: Potential benefits of combining docosahexaenoic acid (DHA), an omega-3 fatty acid with flurbiprofe (Flu), a non-steroidal anti-inflammatory drug in ameliorating obesity remain to be elucidated. This study aimed to investigate the possible protective effects of DHA and Flu, either alone or in combination, against obesity induced metaflammation and to clarify the underlying molecular mechanisms. Methods: Seventy-five male Wistar rats were divided into five groups: normal diet (ND) group, high-carbohy drate high-fat diet (HCHFD) control group, DHA group (HCHFD+200 mg/kg DHA), Flu group (HCHFD+10 mg/kg Flu), and DHA+Flu group (HCHFD+DHA+Flu). Treatments were administered orally daily for 8 consecutive weeks, parallel with the start of diets. Results: Plasma levels of glucose, insulin, and TGs were significantly reduced in DHA, Flu, and DHA+Flu treated groups, while HDL-C concentrations were significantly elevated in the same groups, compared to HCHFD control group. Only Flu and DHA+Flu groups showed a significant decrease in plasma levels of leptin, TC, and LDL-C, relative to HCHFD control group. Concentrations of phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) and resolvin D1 (RvD1) in epididymal adipose tissue (EAT) were significantly increased in the three treated groups, compared with HCHFD control group. Expression of AMPK - subunit in EAT was .1 significantly increased, whereas expression of nuclear factor kappa B (NF- .B) was significantly decreased in EAT of the three treated groups, relative to HCHFD control group. Conclusions: Docosahexaenoic acid-flurbiprofen combination showed an ameliorative effect on obesity-asso ciated metaflammation and its consequences in rats. Objective: Potential benefits of combining docosahexaenoic acid (DHA), an omega-3 fatty acid with flurbiprofe (Flu), a non-steroidal anti-inflammatory drug in ameliorating obesity remain to be elucidated. This study aimed to investigate the possible protective effects of DHA and Flu, either alone or in combination, against obesity induced metaflammation and to clarify the underlying molecular mechanisms. Methods: Seventy-five male Wistar rats were divided into five groups: normal diet (ND) group, high-carbohy drate high-fat diet (HCHFD) control group, DHA group (HCHFD+200 mg/kg DHA), Flu group (HCHFD+10 mg/kg Flu), and DHA+Flu group (HCHFD+DHA+Flu). Treatments were administered orally daily for 8 consecutive weeks, parallel with the start of diets. Results: Plasma levels of glucose, insulin, and TGs were significantly reduced in DHA, Flu, and DHA+Flu treated groups, while HDL-C concentrations were significantly elevated in the same groups, compared to HCHFD control group. Only Flu and DHA+Flu groups showed a significant decrease in plasma levels of leptin, TC, and LDL-C, relative to HCHFD control group. Concentrations of phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) and resolvin D1 (RvD1) in epididymal adipose tissue (EAT) were significantly increased in the three treated groups, compared with HCHFD control group. Expression of AMPK - subunit in EAT was .1 significantly increased, whereas expression of nuclear factor kappa B (NF- .B) was significantly decreased in EAT of the three treated groups, relative to HCHFD control group. Conclusions: Docosahexaenoic acid-flurbiprofen combination showed an ameliorative effect on obesity-asso ciated metaflammation and its consequences in rats. vascularization which leads to areas with lower oxygen availability [6]. Furthermore, adipocytes undergo a profound change in their secretome Obesity is a major health hazard marked by excessive body fat ac profile by an increased expression of pro-inflammatory cytokines and /m2. cumulation and elevated body mass index (BMI) that exceeds 30 kg alterations in the level of adipokines [7]. These changes result in an It is prevalently escalating with a present count of more than 500 undesirable inflammatory cells infiltration [8] associated with an in million having a high risk of morbidity [1] and it is likely to double by creased necrosis of adipocytes [9]. 2040 [2]. The most common cause of obesity was found to be a long This chronic inflammation linked to metabolic cells (metaflamma term imbalance between energy intake and expenditure [3], which tion) is deleterious and leads to local WAT dysfunction and systemic occurs primarily due to sedentary lifestyles and unhealthy dietary ha metabolic complications including insulin resistance, type 2 diabetes, bits, specifically diets rich in saturated fats and carbohydrates [4]. dyslipidemia, etc. [10]. Monotherapies often offer small to moderate White adipose tissue (WAT) plays a crucial endocrine role in bal weight loss benefits, while polytherapies seem to show more promising ancing metabolic homeostasis and inflammation-modulatory activities results in the management of obesity and related comorbidities [11]. beyond the paradigm of fuel storage [5]. During conditions of pro Therefore, development of new therapeutic strategies is of vital im longed over-nutrition, there is an expansion of adipose tissue mass portance [12]. through hypertrophy and hyperplasia, causing a reduction in tissue Flurbiprofen (Flu), a nonsteroidal anti-inflammatory drug (NSAID. |