Hu FB Research Articles

LDL Cholesteryl Oleate

Cholesteryl esters (CE) are synthesized by 2 enzymes, lecithin:cholesterol acyltransferase (LCAT) and acylCoA:cholesterol acyltransferase (ACAT). LCAT functions in the plasma and forms CE in HDL by transferring polyunsaturated fatty acid from phosphatidylcholine to cholesterol. ACAT, which functions intracellularly, uses fatty acid from acylCoA and forms CE enriched in monounsaturated fatty acid. Two isoforms of ACAT are expressed.1 ACAT1 is present in many tissues and produces the CE that are stored intracellularly, whereas ACAT2 is expressed in the intestine and liver and produces the CE that are secreted in chylomicrons and VLDL.2 See page 1396 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Bell et al report that ACAT2 gene deletion prevents hypercholesterolemia and atherosclerosis induced by diets containing 10% saturated or monounsaturated fat in a murine model of high LDL apoB100 only, LDL receptor-deleted (LDLr−/−) mice.3 These mice also had larger LDL particle size and hypertriglyceridemia. They attribute the protection of ACAT2 deficiency to a decrease in LDL particles enriched in CE derived from oleate (monounsaturated). When the diet contains large amounts of monounsaturated fats, ACAT2 activity appears to favor production of VLDL particles containing an excessive amount of cholesteryl oleate,4 and these monounsaturated CE remain associated with the lipoprotein particle when it undergoes conversion to LDL. These findings remind us that CE synthesized in the liver can be a source of CE for LDL, a fact that tends to be overlooked because of the current emphasis on the role of the reverse cholesterol transport pathway and cholesteryl ester transport protein (CETP) in supplying CE to VLDL and ultimately LDL. The Figure illustrates how LCAT, CETP, and ACAT2 function to supply monounsaturated and polyunsaturated CE that can accumulate in LDL. A schematic summary of the pathways that provide cholesteryl esters (CE) for incorporation …

Folate supplementation and cardiovascular disease

Many observational studies have suggested that folate and homocysteine—the intermediate phenotype lowered by folate supplementation—are causally related to coronary heart disease (CHD) and stroke. 1 Rimm EB Willett WC Hu FB et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998; 279: 359-364 Crossref PubMed Scopus (752) Google Scholar Indeed, the evidence was deemed strong enough to recommend inclusion of folate in the “polypill”—the combination tablet championed as a one-stop solution for cardiovascular disease 2 Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003; 326: 1419-1423 Crossref PubMed Google Scholar —and to recommend folate supplements as part of a healthy lifestyle. 3 Willett WC Eat, drink and be healthy: the Harvard Medical School guide to healthy eating. Simon & Schuster, New York2001 Google Scholar Thus the recent finding of no benefit with folate supplementation in NORVIT—the largest trial to date to test the hypothesis that folate supplementation reduces risk of cardiovascular disease—is a clear disappointment. 4 Bønaa KH NORVIT: randomised trial of homocysteine-lowering with B-vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction. European Society of Cardiology, StockholmSept 5, 2005http://www.escardio.org/knowledge/onlinelearning/slides/ESC_Congress_2005/BonaaFP1334.htm Google Scholar

Sugar-Sweetened Beverage Consumption Is Associated With Weight Gain and Incidence of Type 2 Diabetes

Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ, Willett WC, Hu FB: Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA292 : 927-934,2004 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Objective. To examine the association between consumption of sugar-sweetened beverages, weight change, and risk for type 2 diabetes in women. Design. A prospective cohort study. Participants. Study participants were drawn from the 116,671 women aged 22-44 years enrolled in the Nurses' Health Study II. Women lacking dietary or physical activity data or with a history of diabetes, cancer, or cardiovascular disease were excluded. A total of 91,249 women were included in the diabetes analysis. Of these, 51,603 women for whom height and weight data were available were included in the analysis on weight change. Methods. Information on weight and morbidity was collected every 2 years from 1991 through 1999 using a mailed questionnaire. Dietary data were collected through a food frequency questionnaire every 4 years. Women were asked how often, on average over the previous year, they consumed the following beverages: sugar-sweetened soft drinks (“Coke, Pepsi, or other cola with sugar,” “caffeine-free Coke, Pepsi, or other cola with sugar,” and “other carbonated beverages with sugar”); fruit juice (“apple juice,” “orange juice,” grapefruit juice,” and “other juice”); fruit punch; and diet soft drinks (“low-calorie cola with caffeine,” “low-calorie caffeine-free cola,” and “other low-calorie beverages”). The impact of sugar-sweetened soft drink consumption on total calorie intake, weight gain, and incidence of type 2 diabetes was assessed. Similar comparisons were made for fruit punch, fruit juice, and diet soft drink consumption. The mean weight change in groups of women, defined by their consumption pattern for each beverage type from 1991 to … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DSchulze%26rft.auinit1%253DM.%2BB.%26rft.volume%253D292%26rft.issue%253D8%26rft.spage%253D927%26rft.epage%253D934%26rft.atitle%253DSugar-Sweetened%2BBeverages%252C%2BWeight%2BGain%252C%2Band%2BIncidence%2Bof%2BType%2B2%2BDiabetes%2Bin%2BYoung%2Band%2BMiddle-Aged%2BWomen%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.292.8.927%26rft_id%253Dinfo%253Apmid%252F15328324%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.292.8.927&link_type=DOI [3]: /lookup/external-ref?access_num=15328324&link_type=MED&atom=%2Fdiaclin%2F23%2F4%2F150.atom [4]: /lookup/external-ref?access_num=000223429200017&link_type=ISI

Adiponectin. Spectator or Player?

Adiponectin. Spectator or Player?

Adiponectin and Coronary Heart Disease: The Strong Heart Study

To the Editor: The adipocyte secreted protein, adiponectin, is of particular interest in metabolic and vascular disease because of its close associations with insulin sensitivity and obesity.1 Lower levels of adiponectin are associated with later development of type 2 diabetes.2 Recent observations from the Health Professionals Follow-Up Study3 suggest that lower adiponectin concentrations might also be associated with incident myocardial infarction, findings in keeping with prior observations in patients with end-stage renal failure.4 We examined prospective relationships of adiponectin to vascular disease in a case–control series selected from the Strong Heart Study (SHS). The SHS is the largest study of cardiovascular disease in American Indians, a group at particular risk of obesity and type 2 diabetes and in whom an increasing incidence of coronary heart disease (CHD) is seen.5 Cases and controls were selected from the SHS cohort.6 The SHS recruited 4549 volunteers of American Indian heritage from 3 geographic areas (Arizona, North and South Dakota, and Oklahoma).6 Volunteers (59% female) were invited to a study examination on three occasions (SH1, 1988 to 1992; SH2, 1993 to 1995; SH3, 1997 to 1999) and remained under continued surveillance for development of vascular disease as described previously.7,8 Because of availability of plasma samples, baseline data for this study were taken from the second examination (SH2), and participants with prevalent cardiovascular disease at SH2 (definite CHD and stroke), …

AHA Science Advisory. Monounsaturated fatty acids and risk of cardiovascular disease. American Heart Association. Nutrition Committee.

This report summarizes our current understanding of how monounsaturated fatty acids (MUFAs) affect risk for cardiovascular disease (CVD). This is a topic that has attracted considerable scientific interest,1 2 3 in large part because of uncertainty regarding whether MUFA or carbohydrate should be substituted for saturated fatty acids (SFAs) and the desirable quantity of MUFA to include in the diet. MUFAs are distinguished from the other fatty acid classes on the basis of having only 1 double bond. In contrast, polyunsaturated fatty acids (PUFAs) have 2 or more double bonds, and SFAs have none. The position of the hydrogen atoms around the double bond determines the geometric configuration of the MUFA and hence whether it is a cis or trans isomer. In a cis MUFA, the hydrogen atoms are present on the same side of the double bond, whereas in the trans configuration, they are on opposite sides. The American Heart Association Nutrition Committee recently published a scientific statement regarding the relationship of trans MUFA to CVD risk,4 and the present statement, therefore, will be limited to a discussion of dietary cis MUFAs, of which oleic acid ( cis C18:1) comprises ≈92% of cis MUFAs. In the United States, average total MUFA intake is 13% to 14% of total energy intake, an amount that is comparable to (or slightly greater than) SFA intake. In contrast, PUFAs contribute less (ie, 7% of energy). The major emphasis of current dietary guidelines involves replacing SFAs with complex carbohydrates to achieve a total fat intake of ≤30% of calories. There is evidence suggesting that the substitution of MUFA instead of carbohydrate for SFA calories may favorably affect CVD risk.5 6 7 The American Heart Association dietary guidelines for healthy American adults recommend a diet that provides <10% of calories from SFA, up …

Frequent nut consumption reduced the risk of coronary heart disease in women

Hu FB, Stampfer MJ, Manson JE, et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ1998 Nov 14; 317 : 1341 –5. [OpenUrl][1][Abstract/FREE...

Folate and vitamin B 6 from diet and supplements in relation to risk of coronary heart disease among women : Rimm EB, Willett WC, Hu FB, et al. JAMA. 1998;279(5):359–364

Vitamin B6 exists as a family of chemical species that ultimately can be converted metabolically to the coenzyme pyridoxal 5′-phosphate (PLP). PLP serves as a coenzyme in almost all aspects of human metabolism, including amino acid metabolism, one-carbon metabolism, glycogenolysis, and gluconeogenesis. Recent evidence indicates that inflammation suppresses PLP in the plasma and liver. Inflammation also increases vitamin B6 catabolism. However, the mechanistic connection between vitamin B6 insufficiency and chronic disease remains unclear.