Fatty Acid Metabolism and Derived-Mediators Distinctive of PPAR-α Activation in Obese Subjects Post Bariatric Surgery

Abstract

Bariatric surger (BS) is characterized by lipid metabolic changes as a response to the massive release of non-esterified fatty acids (NEFA) from adipose depots. The study aimed at evaluating changes in polyunsaturated fatty acids (PUFA) metabolism and biosynthesis of the lipid mediators N-acylethanolamines (NAE), as indices of nuclear peroxisome proliferator-activated receptor (PPAR)-α activation. The observational study was performed on 35 subjects (27 female, 8 male) with obesity, undergoing bariatric surgery. We assessed plasma FA and NAE profiles by LC-MS/MS, clinical parameters and anthropometric measures before and 1 and 6 months after bariatric surgery. One month after bariatric surgery, as body weight and clinical parameters improved significantly, we found higher plasma levels of N-oleoylethanolamine, arachidonic and a 22:6-n3/20:5-n3 ratio as evidence of PPAR-α activation. These changes corresponded to higher circulating levels of NEFA and a steep reduction of the fat mass. After 6 months 22:6-n3/20:5-n3 remained elevated and fat mass was further reduced. Our data suggest that the massive release of NEFA from adipose tissue at 1-Post, possibly by inducing PPAR-α, may enhance FA metabolism contributing to fat depot reduction and improved metabolic parameters in the early stage. However, PUFA metabolic changes favor n6 PUFA biosynthesis, requiring a nutritional strategy aimed at reducing the n6/n3 PUFA ratio.

FGF21 reflects a responsive adipose tissue-liver axis in both cardiometabolic burden and following metabolic surgery

“…These results align with the understanding that FFAs, which increase due to the insufficient insulin-dependent inhibition of AT-lipolysis in states of insulin resistance, are strong determinants of FGF21 levels [3]. Furthermore, the acute rise in FFAs following metabolic surgery, leading to increased hepatic activation of PPAR-α [36], the key regulator of hepatic FGF21 [37], underscores the dynamic interplay between AT and liver response in the pathophysiology of obesity and weight loss.…”

The circulating and central endocannabinoid system in obesity and weight loss

“…The exact opposite result was found in a study by Zoon et al who found slightly increased levels of AEA and non-significantly altered 2-AG concentrations at an average of 9.2 weeks after RYGB(104). At 6 months after SG or RYGB, Manca et al found a small but significant decrease in AEA levels but unchanged 2-AG levels(103). Mallipedhi et al, on the other hand, found no change in both plasma 2-AG and AEA levels 6 months after SG or biliopancreatic diversion(105).…”

“…RYGB) and found no changes in AEA plasma levels, while 2-AG showed a two-fold increase compared to presurgery level(103). The exact opposite result was found in a study by Zoon et al who found slightly increased levels of AEA and non-significantly altered 2-AG concentrations at an average of 9.2 weeks after RYGB(104).…”

Identification of a Fatty Acid for Diagnosing Non-Alcoholic Steatohepatitis in Patients with Severe Obesity Undergoing Metabolic Surgery

“…A possible explanatory mechanism for this effect could be that the progression of the arachidonic acid cascade was inhibited by the metabolic improvement caused by LSG, resulting in an increase in substrates prior to arachidonic acid production and increased reuptake of FFAs. Furthermore, it has been reported that FAs, such as phospholipids, may induce the activation of peroxisome proliferator-activated receptor alpha (PPAR-α), thereby inhibiting FA oxidation and contributing to decreased fat deposition in tissues [ 44 ]. Sustained induction of PPAR-α has been reported to suppress inflammation by inducing I kappa B kinase alpha, an inhibitory protein of NF-κB [ 44 ].…”

“…Furthermore, it has been reported that FAs, such as phospholipids, may induce the activation of peroxisome proliferator-activated receptor alpha (PPAR-α), thereby inhibiting FA oxidation and contributing to decreased fat deposition in tissues [ 44 ]. Sustained induction of PPAR-α has been reported to suppress inflammation by inducing I kappa B kinase alpha, an inhibitory protein of NF-κB [ 44 ]. This effect may inhibit the progression of the arachidonic acid cascade and may also be involved in decreased inflammation in NASH.…”