Abstract
Obesity, in particular visceral obesity, has become a major worldwide health problem. Obesity increases cardiovascular risk through risk factors such as elevated fasting TG, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels, and high blood pressure. The typical dyslipidemia of obesity consists of increased TG and FFA, decreased HDL-C with HDL dysfunction, and normal or slightly increased LDL-C with increased small dense LDL. The concentrations of plasma apolipoprotein (apo) B are also often increased, partly due to the hepatic overproduction of apo B-containing lipoproteins. A delayed metabolism of intestinal-derived lipoproteins is usually seen in obesity. All lipoprotein abnormalities typically associated with visceral obesity in obesity carry an elevated pro-atherogenic potential. In particular, the prolonged presence in circulation of remnants of TG-rich lipoproteins and the preponderance of small dense LDLs are considered to play the most relevant role. Even though the reduction of LDL-C is the main target of treatment of dyslipidemia in obesity, apo B or non-HDL-C levels are recommended as secondary treatment targets. Treatment of dyslipidemia in obesity should be aimed at weight loss by increased exercise and improved dietary habits with a reduction in total calorie intake and reduced SFA intake. Medical therapy can be initiated if lifestyle changes are insufficient. Statins are the primary lipid-lowering drugs with effective reductions in LDL and remnant cholesterol levels. Moreover, the addition of fibrates may be considered in case of residual elevated TG and reduced HDL-C levels.
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Keywords
- Cholesteryl Ester Transfer Protein
- Resistant Starch
- Cholesterol Efflux
- Visceral Obesity
- Postprandial Lipemia
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
1 Introduction
Obesity is a major public health problem due to its increasing prevalence in both developed and developing countries [1]. The increase in the prevalence of obesity is occurring not only in adults but also in children and adolescents, in whom relative increases in obesity prevalence are particularly striking [2]. The exploding obesity epidemic has put this emerging risk factor at the front of cardiovascular risk assessment and management. Accordingly, the American Heart Association has published several position papers to document and emphasize the health hazards of obesity [3]. Although it is clear that more obesity is associated with more type 2 diabetes mellitus and with a greater risk of developing a variety of cardiovascular health outcomes, this condition is complex and heterogeneous as a phenotype. It is well established that visceral obesity may be a driver of an increased risk of coronary heart disease (CHD). Recent reviews of the strength of the prospective relationship between adiposity in adult life (measured as body mass index [BMI]) and CHD risk have suggested that a 1 kg/m2 higher BMI is associated with increases in CHD risk of approximately 7–5 % [4–6]. The association is largely independent of confounding by cigarette smoking [5] but is partly mediated by blood pressure and dyslipidemia. Therefore, the current review will mainly focus on the changes in lipoprotein metabolisms seen in obesity and their implication into atherogenesis. In addition, the pharmacological and non-pharmacological interventions to control dyslipidemia in obesity will be examined.
2 Dyslipidemia in Obesity: The Pathophysiological Mechanisms
Obesity significantly affects lipoprotein metabolism. The typical plasma lipid abnormality associated with visceral obesity is characterized by increased plasma concentration of triglycerides (TG), reduced concentration of high-density lipoprotein cholesterol (HDL-C), and qualitative alteration of low-density lipoprotein (LDL) fraction due to the preponderance of the small and dense LDL (sdLDL) (Fig. 12.1). There is a large agreement that these alterations have a great pro-atherogenic potential so that this form of dyslipidemia has been, more appropriately, defined as atherogenic dyslipidemia (AD) [7].
It is thought that atherogenic dyslipidemia is caused by a multiple array of metabolic abnormalities such as: (1) increased production of TG-rich lipoproteins from the liver and intestine, (2) increased cholesterol synthesis, (3) delayed clearance of TG-rich lipoproteins, and (4) increased HDL catabolism. However, an important question is which of these abnormalities is the more relevant in determining the typical lipid phenotype of AD. Several lines of evidence indicate that the pivotal role is played by the increased production of very-low-density lipoproteins (VLDL) by the liver. In vivo turnover studies have, in fact, shown that the dominant feature of AD is the increased production rate of VLDL-apo B by the liver, mainly as large VLDL particles (VLDL1) [8]. The VLDL1 production rate is the strongest determinant of TG concentration in the plasma and is significantly related to indices of insulin sensitivity [8].
The enhanced influx of VLDL particles into the bloodstream not only determines hypertriglyceridemia but is the major cause of the other lipid abnormalities of AD since it will lead to delayed clearance of the TG-rich lipoproteins and formation of sdLDL [9, 10]. In the presence of hypertriglyceridemia, the cholesterol-ester content of LDL decreases, whereas that of TG increases due to the enhanced activity of the cholesteryl ester transfer protein (CETP), the circulating enzyme that promotes the exchange of cholesterol esters (CE) with TGs between VLDL and LDL. However, the increased TG content within the LDL is hydrolyzed by hepatic lipase, which leads to the formation of sdLDL particles [11]. The development of sdLDL in obesity is mainly due to increased TG concentrations and does not depend on total body fat mass [12].
Lipolysis of TG-rich lipoproteins is also impaired in obesity by reduced activity of lipoprotein lipase (LPL), the enzyme that regulated the lipolysis of TGs in VLDL and intestinal-derived chylomicron [13]. Studies using stable isotopes have shown a decreased catabolism of chylomicron remnants in obese subjects with the waist/hip ratio as the best predictor for the fractional catabolic rate [14]. Additionally, prolonged postprandial lipemia leads to elevated levels of FFA, resulting in detachment of LPL from its endothelial surface [15], further reducing the postprandial catabolism of TG-rich lipoproteins. It has been well demonstrated that postprandial hyperlipidemia with accumulation of atherogenic remnants is especially linked to visceral obesity [16]. Van Oostrom et al. have shown that diurnal triglyceridemia in obese subjects correlates better to waist circumference than to body mass index [17], which is in agreement with the hypothesis that the distribution of adipose tissue modulates postprandial lipemia. There are reports suggesting that also the metabolism of LDL might be altered in obese individuals mainly due to the reduced expression of LDL receptors [18].
The increased number of remnants of chylomicrons and VLDL together with impaired lipolysis in obesity also significantly affects the HDL metabolism. As mentioned before, the increased number of TG-rich lipoproteins results in increased CETP activity, which exchanges CE from HDL for TG from VLDL and LDL [19]. Moreover, lipolysis of these TG-rich HDLs occurs by hepatic lipase resulting in small HDL with a reduced affinity for apo A-I, which leads to dissociation of apo A-I from HDL. This will ultimately lead to lower levels of HDL-C and a reduction in circulating HDL particles with impairment of reversed cholesterol transport [20].
3 The Atherogenic Potential of Lipoprotein Abnormalities in Obesity
The resulting effect of all abovementioned abnormalities in the lipoprotein metabolism in obesity is the accumulation of pro-atherogenic lipoproteins and the impairment of HDL function. In fact, sdLDLs are relatively slowly metabolized with a 5-day (instead of 2-day) residence time, which enhances its atherogenicity [11]. In addition, sdLDLs have an increased affinity for arterial proteoglycans resulting in enhanced subendothelial lipoprotein retention [21]. Finally, it has been described that sdLDLs are more susceptible to oxidation, in part due to less free cholesterol and anti-oxidative content [19]. Remnants of chylomicrons and VLDL are also involved in the development of atherosclerosis. Several investigations have documented an association between TG-rich lipoproteins and remnant cholesterol levels with the presence of coronary atherosclerosis [22]. This has been explained by the fact that chylomicron remnants and LDL may migrate into the vessel wall and become trapped in the subendothelial space where they can be taken up by monocytes/macrophages [23]. This mechanism may be facilitated by the fact that subendothelial remnants of chylomicrons and VLDL do not need to become modified to allow uptake by scavenger receptors of macrophages in contrast to native LDL [23]. Even though LDL particles migrate more easily than chylomicron remnants into the subendothelial space, the number of migrated particles does not necessarily translate into more cholesterol deposition since chylomicron remnants contain approximately 40 times more cholesterol per particle than LDL [23]. Other mechanisms of remnant-mediated atherogenesis, which may play a role in obesity, comprise the postprandial activation of leukocytes, generation of oxidative stress, and production of cytokines [24]. On the other side, the abnormality in HDL concentration and composition is thought to have an important impact in deteriorating the contribution of this particle to the cholesterol efflux from the cells. The capacity of cholesterol efflux, which is the first step in the reverse cholesterol transport, has been associated with increased risk of coronary artery disease and with the flow-mediated vasodilation in diabetic obese patients [25]. It has been also reported that HDL isolated from obese diabetic patients shows a reduced capacity to promote ex vivo cholesterol efflux from cells and that this may be related to a lower expression of ABCA1, which is the membrane transporter responsible for the first step of transfer of cholesterol from cell membrane to HDL particle [26].
4 Lipid Targets for Treatment of Dyslipidemia in Obesity
The EAS/ESC guidelines recommend testing lipids in obese subjects in order to assess their cardiovascular risk [27]. However, the necessity to initiate pharmacological treatment next to lifestyle intervention in obese subjects with dyslipidemia depends on the comorbidity, the potential underlying primary lipid disorders, and the calculated cardiovascular risk [13, 27]. Irrespective of increased body weight, LDL-C is the primary target for the treatment of dyslipidemia in obesity [27] (Table 12.1). Nevertheless, the presence of obesity can affect treatment targets since obesity may contribute to increased remnant cholesterol, higher TG levels, and lower HDL-C concentrations. Therefore, apo B or non-HDL-C levels are recommended as secondary treatment targets next to LDL-C levels in the presence of AD [13, 27]. Apo B represents the total number of atherogenic particles (chylomicrons, chylomicron remnants, VLDL, IDL, and LDL), whereas non-HDL-C represents the amount of cholesterol in both the TG-rich lipoproteins and LDL. Recently, a meta-analysis has shown that implementation of non-HDL-C or apo B as treatment target over LDL-C would prevent an additional 300,000–500,000 cardiovascular events in the US population over a 10-year period [28]. However, others did not describe any benefit of apo B or non-HDL-C over LDL-C levels to assess cardiovascular risk [29]. The treatment target for non-HDL-C should be 30 mg/dl higher than the target for LDL-C, which corresponds with non-HDL-C levels of 160 mg/dl and 130 mg/dL for subjects at moderate and high risk, respectively. Treatment targets for apo B are approximately 0.80–1.00 g/L [27]. Specific treatment targets for TG levels are unavailable, especially since TGs are highly variable and increase during the day. However, pharmacological interventions to lower specifically TG should be initiated when TG levels exceed 800 mg/dl to reduce the risk for pancreatitis [13, 30].
5 Pharmacological and Non-pharmacological Interventions for Dyslipidemia in Obesity
Treatment of obesity-associated dyslipidemia should be focused on lifestyle changes including weight loss, physical exercise, and a healthy diet. Lifestyle changes synergistically improve insulin resistance and dyslipidemia [31]. Weight loss has been demonstrated to markedly reduce fasting and non-fasting TG concentrations, which can be attributed to an increase in LPL activity, and thereby an increased catabolism of TG-rich lipoproteins [32]. Besides reductions in fasting and non-fasting TG, a small reduction in LDL-C can be expected upon weight loss, which may be attributed to increased LDL receptor activity. A weight loss of 4–10 kg in obese subjects resulted in a 12 % reduction in LDL-C and a 27 % increase in LDL receptor mRNA levels [33]. The type of dietary fat also affects postprandial lipemia. In obese men, a moderate weight loss (approximately 10 %) induced by a diet low on carbohydrates and saturated (SFA) and high on monounsaturated fatty acids (MUFA), resulted in a 27–46 % reduction in postprandial TG levels [34]. Long-term intervention with MUFA resulted in a reduction in postprandial inflammation when compared to a diet rich in SF in patients with metabolic syndrome (MetS) [35].
Physical exercise has been shown to increase LPL and hepatic lipase activity, which stimulates TG lipolysis [36]. The mechanism of exercise-induced LPL activity remains unclear, but it was hypothesized that exercise stimulates especially muscular LPL activity. A 12-week walking program supplemented with fish oil (1,000 mg eicosapentaenoic acid and 700 mg docosahexaenoic acid daily) in subjects with the MetS resulted in lower fasting TG and decreased the postprandial response of TG and apoB48 [37]. More interestingly, physical activity has been reported to favorably influence ectopic fat accumulation (mainly in the liver) in obese individuals. Exercise training for 16 weeks in obese subjects with non-alcoholic fatty liver disease (NAFLD) resulted in a small reduction in intrahepatic TG content, although no changes in VLDL-TG or apoB100 secretion were observed [38]. Exercise-induced reductions in intrahepatic TG content have also been reported even in the absence of weight loss [39]. Moreover, intrahepatic TG content was reduced in overweight men after a low-fat diet for 3 weeks, whereas a high-fat diet increased intrahepatic TG [40]. The plasma TG-lowering effect of exercise and weight loss is the most consistent finding in studies concerning blood lipids [41], whereas increasing HDL-C levels by exercise remains controversial, especially in those subjects with high TG and low HDL-C levels [42]. Other dietary factors such as dietary fibers have been shown to improve nutrient absorption and have also been linked to insulin metabolism. Daily intake of resistant starch from bread, cereals, vegetables, and pastas is approximately 5 g/day in the Western world, which is highly insufficient for potential health benefits [43]. Recently, a randomized study in 15 insulin-resistant subjects has shown that 8 weeks of resistant starch supplementation (40 g/day) improved insulin resistance and subsequently FFA metabolism. Resistant starch ingestion resulted in lower fasting FFA concentrations and increased TG lipolysis by enhanced expression of genes like LPL coupled with increased FFA uptake by skeletal muscle [44]. However, no effect of resistant starch supplementation was observed on TG and cholesterol concentrations [44].
Unfortunately, lifestyle modifications are often insufficient to achieve weight loss and improvement of dyslipidemia, and, therefore, pharmacological treatment must be considered. The effects on dyslipidemia of antiobesity drugs are very limited, if present. A recent meta-analysis concerning antiobesity drugs reported a mean weight loss of 3.13 kg, but a very little improvement of dyslipidemia [45]. Orlistat, which reduces the lipolysis of TG within the gastrointestinal system and thus prevents absorption of intestinal fat by 30 %, showed only a modest reduction in LDL-C of 8 mg/dl. Sibutramine, which increases the sensation of satiety by modulating the central nervous system, showed a 12 mg/dl reduction in TG, whereas rimonabant did not show any lipid improvements [45]. Conversely, bariatric surgery-induced weight loss has been associated with decreased TG and increased HDL-C levels [46].
Obesity-associated dyslipidemia may well be treated with specific hypolidemic medications (Table 12.1). Statins are the first-choice agents to reduce LDL-C, non-HDL-C, and/or apo B. However, statins lower TG only marginally and do not fully correct the characteristic dyslipidemia seen in obesity, which may contribute to the residual risk after initiating statin therapy [47]. Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), which is the rate-limiting step in the hepatic cholesterol synthesis. This, in turn, increases the fractional catabolic rate of VLDL and LDL together with a slight reduction in hepatic secretion of VLDL. Therefore, statins lower both remnant cholesterol and LDL-C levels [48]. Recently, strategies for combination therapies with statins to achieve even lower cholesterol levels have been reviewed [47]. Combinations can be made with ezetimibe, which inhibits the intestinal cholesterol absorption by interaction with NPC1L1, which results in an additional 20 % lowering effect on LDL-C, but without affecting TG or HDL-C concentrations [49]. On the contrary, fibrates are primarily indicated in the case of hypertriglyceridemia, and they reduce TG by approximately 30 % and LDL-C by 8 %, whereas HDL-C is increased by an average of 9 % [50]. Fibrates are peroxisome proliferator-activated receptor-α agonists, which transcriptionally regulate lipid metabolism-related genes. Fibrates as monotherapy have been shown to reduce cardiovascular mortality, especially in subjects with characteristics of the MetS with TG levels >190 mg/dl [51]. However, there is controversy about the effectiveness of fibrate therapy on top of statin therapy since the ACCORD trial was unable to confirm a beneficial effect on cardiovascular end points by fenofibrate combined with statins in diabetic patients [52]. Nevertheless, It must be mentioned that subgroup analyses suggested a beneficial effect of combination therapy of fibrates with statins in patients with AD [52]. Omega-3 fatty acids, which decrease the hepatic synthesis and accumulation of TG [53], have been shown to reduce plasma TG by 25–30 % by effectively reducing the hepatic secretion of VLDL in insulin-resistant subjects [54]. Omega-3 fatty acids have also been shown to increase the conversion of VLDL into IDL, which suggests an additional benefit for combining omega-3 fatty acids with statins by increased catabolism of VLDL, IDL, and LDL. Drugs that increase insulin sensitivity like metformin or thiazolidinedione derivatives have no or minimal effects on lipoprotein profile in obesity [55].
6 Conclusions
The pathophysiology of the typical dyslipidemia observed in obesity is multifactorial and includes hepatic overproduction of VLDL, decreased circulating TG lipolysis and impaired peripheral FFA trapping, increased FFA fluxes from adipocytes to the liver and other tissues, and formation of sdLDL. Treatment should be aimed at weight loss by increasing exercise and improving dietary habits with a reduction in total calorie intake and reduced SFA intake. Medical therapy can be initiated if lifestyle changes are insufficient. Statins are the primary lipid-lowering drugs with effective reductions in LDL and remnant cholesterol levels. Moreover, the addition of fibrates may be considered in case of residual dyslipidemia in subjects with diabetes mellitus, elevated TG, and reduced HDL-C levels. Apo B and/or non-HDL-C concentrations reflect the atherogenic lipid burden more accurately than LDL-C alone in obesity and should be used as treatment targets.
References
Knight JA (2011) Diseases and disorders associated with excess body weight. Ann Clin Lab Sci 41:107–121
Ebbeling CB, Pawlak DB, Ludwig DS (2002) Childhood obesity: public-health crisis, common sense cure. Lancet 360:473–482
Poirier P, Giles TD, Bray GA, American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism et al (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113:898–918
Whitlock G, Lewington S, Mhurchu CN (2002) Coronary heart disease and body mass index: a systematic review of the evidence from larger prospective cohort studies. Semin Vasc Med 2:369–381
Bogers RP, Bemelmans WJ, Hoogenveen RT et al (2007) Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med 167:1720–1728
Whitlock G, Lewington S, Sherliker P et al (2009) Body-mass index and cause-specific mortality in 900.000 adults: collaborative analyses of 57 prospective studies. Lancet 373:1083–1096
Grundy SM (2006) Atherogenic dyslipidemia associated with metabolic syndrome and insulin resistance. Clin Cornerstone 8(Suppl 1):S21–S27
Adiels M, Borén J, Caslake MJ et al (2005) Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia. Arterioscler Thromb Vasc Biol 25:1697–1703
Castro Cabezas M, de Bruin TW, Jansen H et al (1993) Impaired chylomicron remnant clearance in familial combined hyperlipidemia. Arterioscler Thromb 13:804–814
Hokanson JE, Krauss RM, Albers JJ et al (1995) LDL physical and chemical properties in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 15:452–459
Packard CJ (2003) Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein. Biochem Soc Trans 31:1066–1069
Tchernof A, Lamarche B, Prud’Homme D et al (1996) The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 19:629–637
Klop B, Jukema JW, Rabelink TJ, Castro Cabezas M (2012) A physician’s guide for the management of hypertriglyceridemia: the etiology of hypertriglyceridemia determines treatment strategy. Panminerva Med 54:91–103
Taskinen MR, Adiels M, Westerbacka J et al (2011) Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects. Arterioscler Thromb Vasc Biol 31:2144–2150
Karpe F, Olivecrona T, Walldius G, Hamsten A (1992) Lipoprotein lipase in plasma after an oral fat load: relation to free fatty acids. J Lipid Res 33:975–984
Couillard C, Bergeron N, Prud’homme D, Bergeron J et al (1998) Postprandial triglyceride response in visceral obesity in men. Diabetes 47:953–960
Van Oostrom AJ, Castro Cabezas M, Ribalta J et al (2000) Diurnal triglyceride profiles in healthy normolipidemic male subjects are associated to insulin sensitivity, body composition and diet. Eur J Clin Invest 30:964–971
Mamo JC, Watts GF, Barrett PH et al (2001) Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression? Am J Physiol Endocrinol Metab 281:E626–E632
Subramanian S, Chait A (2012) Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 1821:819–825
Deeb SS, Zambon A, Carr MC et al (2003) Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. J Lipid Res 44:1279–1286
Tabas I, Williams KJ, Boren J (2007) Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116:1832–1844
Jorgensen AB, Frikke-Schmidt R, West AS et al (2012) Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J doi:10.1093/eurheartj/ehs431
Proctor SD, Vine DF, Mamo JC (2002) Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis. Curr Opin Lipidol 13:461–470
Van Oostrom AJ, van Wijk J, Castro Cabezas M (2004) Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis. Drugs 64:19–41
Zhou H, Shiu SW, Wong Y, Tan KC (2009) Impaired serum capacity to induce cholesterol efflux is associated with endothelial dysfunction in type 2 diabetes mellitus. Diabetes Vasc Dis Res 6:238–243
Patel DC, Albrecht C, Pavitt D et al (2011) Type 2 diabetes is associated with reduced ATP-binding cassette transporter A1 gene expression, protein and function. PLoS One 6:e22142
Catapano AL, Reiner Z, de Backer G et al (2011) ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 217:1–44
Sniderman, AD, Williams, K, Contois, JH, et al (2011) A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ. Cardiovasc. Qual. Outcomes 4:337–345
Boekholdt, SM, Arsenault, BJ, Mora, S, et al (2012) Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: A meta-analysis. JAMA 307:1302–1309
Brunzell JD (2007) Clinical practice. Hypertriglyceridemia. N Engl J Med 357:1009–1017
Klop B, Castro Cabezas M (2012) Chylomicrons: a key biomarker and risk factor for cardiovascular disease and for the understanding of obesity. Curr Cardiovasc Risk Rep 6:27–34
Patalay M, Lofgren IE, Freake HC et al (2005) The lowering of plasma lipids following a weight reduction program is related to increased expression of the LDL receptor and lipoprotein lipase. J Nutr 135:735–739
James AP, Watts GF, Barrett PH et al (2003) Effect of weight loss on postprandial lipemia and low-density lipoprotein receptor binding in overweight men. Metabolism 52:136–141
Maraki MI, Aggelopoulou N, Christodoulou N et al (2011) Lifestyle intervention leading to moderate weight loss normalizes postprandial triacylglycerolemia despite persisting obesity. Obesity (Silver Spring) 19:968–976
Cruz-Teno C, Perez-Martinez P, Delgado-Lista J (2012) Dietary fat modifies the postprandial inflammatory state in subjects with metabolic syndrome: the LIPGENE study. Mol Nutr Food Res 56:854–865
Ferguson MA, Alderson NL, Trost SG et al (1998) Effects of four different single exercise sessions on lipids, lipoproteins, and lipoprotein lipase. J Appl Physiol 85:1169–1174
Slivkoff-Clark KM, James AP, Mamo JC (2012) The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men. Nutr Metab (Lond) 9:9. doi:10.1186/1743-7075-9-9
Sullivan S, Kirk EP, Mittendorfer B, Patterson BW, Klein S (2012) Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology 55:1738–1745
Magkos F (2010) Exercise and fat accumulation in the human liver. Curr Opin Lipidol 21:507–517
van Herpen NA, Schrauwen-Hinderling VB, Schaart G et al (2012) Three weeks on a high-fat diet increases intrahepatic lipid accumulation and decreases metabolic flexibility in healthy overweight men. J Clin Endocrinol Metab 96:E691–E695
Mestek ML (2009) Physical activity, blood lipids, and lipoproteins. Am J Lifestyle Med 3:279–283
Thompson PD, Rader DJ (2001) Does exercise increase HDL cholesterol in those who need it the most? Arterioscler Thromb Vasc Biol 21:1097–1098
Maki KC, Pelkman CL, Finocchiaro ET et al (2012) Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men. J Nutr 142:717–723
Robertson MD, Wright JW, Loizon E et al (2012) Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome. J Clin Endocrinol Metab 97:3326–3332
Zhou YH, Ma XQ, Wu C et al (2012) Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. PLoS One 7:e39062. doi:10.1371/journal.pone.0039062
Aron-Wisnewsky J, Julia Z, Poitou C et al (2011) Effect of bariatric surgery-induced weight loss on SR-BI-, ABCG1-, and ABCA1-mediated cellular cholesterol efflux in obese women. J Clin Endocrinol Metab 96:1151–1159
Watts GF, Karpe F (2011) Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart 97:350–356
Chan DC, Watts GF (2011) Dyslipidaemia in the metabolic syndrome and type 2 diabetes: pathogenesis, priorities, pharmacotherapies. Expert Opin Pharmacother 12:13–30
Dujovn CA, Williams CD, Ito MK (2011) What combination therapy with a statin, if any, would you recommend? Curr Atheroscler Rep 13:12–22
Rubenfire M, Brook RD, Rosenson RS (2010) Treating mixed hyperlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events. Am J Med 123:892–898
Tenenbaum A, Fisman EZ (2012) Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovasc Diabetol. 11:125 doi:10.1186/1475-2840-11-125
Ginsberg HN, Elam MB, Lovato LC et al (2010) Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362:1563–1574
Watts GF, Chan DC, Ooi EM et al (2006) Fish oils, phytosterols and weight loss in the regulation of lipoprotein transport in the metabolic syndrome: lessons from stable isotope tracer studies. Clin Exp Pharmacol Physiol 33:877–882
Chan, DC, Watts, GF, Barrett, PH, et al (2002) Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes 51:2377–2386
Van Wijk JP, de Koning EJ, Martens EP, Rabelink TJ (2003) Thiazolidinediones and blood lipids in type 2 diabetes. Arterioscler Thromb Vasc Biol 23:1744–1749
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Arca, M. (2015). Dyslipidemia and Cardiovascular Risk in Obesity. In: Lenzi, A., Migliaccio, S., Donini, L. (eds) Multidisciplinary Approach to Obesity. Springer, Cham. https://doi.org/10.1007/978-3-319-09045-0_12
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