Effects Of Unsaturated Fatty Acids On Lipid Metabolism And Fatty Acid Distribution In Obese Patients

With the rapid economic growth and improvement of living conditions,excessive energy intake has led to the increasing number of obese patients.Obesity has become one of the nonnegligible problems in public health,seriously threatening human health and social development.Dietary interventions based on personalized healthy foods have become a hotspot of cutting-edge research in the field of food and nutritional sciences and are expected to play an active role in the prevention and treatment of obesity.In dietary interventions for obesity,the ratio of linoleic acid(C18:2 n-6,LA)to alpha-linolenic acid(C18:3 n-3,ALA)in dietary fat has been the focus of increasing research.In mammals,ALA and LA share the same metabolic pathway and compete with each other,so the dietary LA/ALA ratio is critical for obesity.Although the role of LA and ALA in obesity and related metabolic diseases has been widely reported,the results of these studies are variable and in some cases opposite.To elucidate the relationship between LA/ALA ratio and obesity and related metabolic diseases,differences in plasma fatty acids between obese patients and healthy subjects were analyzed in a casecontrol study.Then meta-analysis was used to explore the effects of dietary oleic acid(C18:1n-9,OA)and LA/ALA ratio on obesity and related metabolic indicators.Finally,the effects of LA/ALA ratio on lipid metabolism and fatty acid distribution in obese mice were further analyzed by animal experiments.The main findings of this study are as follows:(1)The differences in plasma fatty acid profiles between obese and normal-weight subjects were systematically studied by case-control analysis.There was no significant change in the contents of arachidonic acid(C20:4 n-6,AA),eicosapentaenoic acid(C20:5 n-3,EPA),docosahexaenoic acid(C20:6 n-3,DHA)and ultra-long chain saturated fatty acids.The plasma total fatty acid concentrations were significantly elevated in most obese populations,as reflected almost uniformly in all types of fatty acids.Analyzed by saturation levels,plasma saturated fatty acid(SFA),monounsaturated fatty acid(MUFA)and polyunsaturated fatty acid(PUFA)contents of obese people were higher than those of control group,but the proportion did not change.In addition,the proportion of SFA in plasma phospholipids and the n-6/n-3PUFA ratio increased in obese people,while the proportion of MUFA decreased.Elevated myristic acid(C14:0,MA),palmitoleic acid(C16:1 n-7,POA),stearic acid(C18:0,SA),and dihomo-gamma-linolenic acid(C20:3 n-6,DGLA),and lowered OA and DHA was associated with obesity risk.DGLA is the only fatty acid whose proportion in both plasma whole lipids and plasma phospholipids is significantly increased.Combined with the metabolic pathway of PUFA,the Δ5 and Δ6 desaturases in plasma phospholipids may be biomarkers of metabolic disorders in obesity.These findings suggest that different fatty acids have different regulatory effects on obesity status,and among them,n-6 PUFA is the most relevant to obesity.(2)The oleic acid-rich diet had a small effect on obesity and related metabolic markers,significantly reducing only C-reactive protein and systolic blood pressure.Thirty-one studies involving 1634 participants were analyzed to assess the effects of dietary interventions for OA on obesity and related metabolic markers.The results showed that increasing dietary OA intake significantly reduced C-reactive protein(CRP)(SMD=-0.11,95% CI:-0.21,-0.01;P=0.038)and systolic blood pressure(SMD=-0.21,95% CI:-0.42,-0.01;P=0.042).There was no significant effect on any of the other indicators.Subgroup analyses were performed for age,BMI,smoking habits,sex,duration,OA dose,health status,and initial baseline concentrations of markers.OA contributed to the reduction of CRP concentrations in people with higher initial CRP concentrations,whereas dietary OA intake did not reduce CRP concentrations when initial CRP concentrations were low.(3)The relationship between a low-ratio LA/ALA diet and obesity and related metabolic indicators was explored.Data from 39 randomized controlled trials involving 2,145 participants were systematically analyzed by means of meta-analysis regarding the effects of different ratio LA/ALA diets on physical indicators,lipids,blood glucose,blood pressure and inflammatory factors.The results showed that the diet with low-ratio LA/ALA significantly reduced waist circumference(WMD:-0.76 cm,95%CI:-2.60 to 1.07,P=0.414),triglyceride(WMD:-0.05mmol/L,95%CI:-0.09 to 0.00,P=0.049),cholesterol(WMD:-0.09 mmol/L,95%CI:-0.17 to-0.01,P=0.031),low-density lipoprotein cholesterol(WMD:-0.08 mmol/L,95%CI:-0.13 to-0.02,P=0.007),diastolic blood pressure(WMD:-1.84 mm Hg,95%CI:-3.10 to-0.58,P=0.004)and IL-6(SMD:-0.22,95%CI:-0.40 to-0.03,P= 0.020).Subgroup analysis showed that cholesterol and low-density lipoprotein decreased significantly when LA/ALA ratio was in the range of 1-5.Waist circumference and diastolic blood pressure were significantly lower at LA/ALA ratios less than 1.(4)The effect mechanism of low-ratio LA/ALA diet on lipid metabolism in mice was investigated.The effects of high-fat diets with different ratios of LA/ALA on body weight,organ indices,biochemical parameters,liver function,hepatic lipids,gene expression,and intestinal flora were evaluated in mice.The results showed that the low-ratio LA/ALA diet reduced body weight by 7.80%,significantly reduced liver index by 11.3%,and inhibited the elevation of plasma triglycerides and blood glucose caused by the high-fat diet in mice that were obese on the high-fat diet.Triglyceride and cholesterol levels were reduced in the livers of mice,and the number of hepatic fat vacuoles was decreased.The ratio of aspartate transaminase to alanine transaminase was reduced by 12.5%,and superoxide dismutase content was elevated by 19.2%.The low-ratio LA/ALA improved the oxidative stress and damage to the liver caused by high-fat diet,increased the level of antioxidant enzymes in the liver,and reduced the probability of hepatic lipid deposition and steatosis.Decreased intestinal Firmicutes/Bacteroidota ratio and reduced abundance of obesity-associated flora in mice on a low-ratio LA/ALA diet regulated the structure of the intestinal flora,thereby improving lipid metabolism in the body.The results of gene expression levels showed that the improvement of lipid metabolism by the low-ratio LA/ALA diet was achieved by up-regulating the expression levels of the lipid oxidative catabolic pathway PPAR-α/ACOX1 and down-regulating the expression levels of the lipid synthesis pathway SREBP-1c/FAS.(5)The fatty acid composition of mouse organs was studied as influenced by the LA/ALA ratio of dietary fat.Fatty acid composition of plasma erythrocytes and eight organs(liver,perienteric fat,epidildyma fat,perirenal fat,spleen,brain,heart,and gastrocnemius muscle)was analyzed by gas phase.It was found that plasma erythrocytes and organs were basically consistent with the trend of dietary fatty acids.The fatty acid composition of adipose tissue was more closely related to that of dietary intake and better reflected dietary fatty acid composition.The low-ratio LA/ALA group significantly increased the content of ALA and its downstream derivative DHA in plasma erythrocytes and eight organs,including liver,and had a high correlation.The accumulation of linoleic acid was more significant in abdominal fat,and the diet with high-ratio LA/ALA resulted in a more pronounced effect on LA deposition.The correlation between fatty acids in the main organs of lipid metabolism(liver and abdominal fat)and fatty acids in the corresponding dietary fat was more pronounced with the intervention of different ratios LA/ALA.High-ratio LA/ALA diet enhanced competitive conversion of LA to GLA and AA in liver and abdominal fat,and low-ratio LA/ALA diet inhibited conversion of LA to GLA,DGLA,and AA in liver and abdominal fat.