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Current Obesity Reports
Erschienen in: Current Obesity Reports 4/2016

29.09.2016 | Metabolism (J Proietto, Section Editor)

Dyslipidemia: Obese or Not Obese—That Is Not the Question

verfasst von: David H. Ipsen, Pernille Tveden-Nyborg, Jens Lykkesfeldt

Erschienen in: Current Obesity Reports | Ausgabe 4/2016

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Abstract

Purpose of Review

Purpose of review: It is becoming increasingly clear that some obese individuals do not develop dyslipidemia and instead remain healthy, while some normal weight individuals become dyslipidemic and unhealthy.

Recent Findings

The present review examines the similarities and differences between healthy and unhealthy individuals with and without obesity and discusses putative underlying mechanisms of dyslipidemia.

Summary

The presence of dyslipidemia and compromised metabolic health in both lean and obese individuals suggests that the obese phenotype per se does not represent a main independent risk factor for the development of dyslipidemia and that dyslipidemia, rather than obesity, may be the driver of metabolic diseases. Notably, adipose tissue dysfunction and ectopic lipid deposition, in particular in the liver, seems a common trait of unhealthy individuals.
Literatur
1.
2.
Franssen R, Monajemi H, Stroes ES, et al. Obesity and dyslipidemia. Med Clin North Am. 2011;95(5):893–902.CrossRefPubMed
3.
Bays HE, Toth PP, Kris-Etherton PM, et al. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013;7(4):304–83.CrossRefPubMed
4.
Moore JB. Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome. Proc Nutr Soc. 2010;69(2):211–20.CrossRefPubMed
5.
Navarro E, Funtikova AN, Fito M, et al. Can metabolically healthy obesity be explained by diet, genetics, and inflammation? Mol Nutr Food Res. 2015;59(1):75–93.CrossRefPubMed
6.
Badoud F, Perreault M, Zulyniak MA, et al. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 2015;29(3):748–58.CrossRefPubMed
7.
8.
Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–223.CrossRefPubMedPubMedCentral
9.
10.
11.
Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92(3):1023–33.CrossRefPubMed
12.
Gagnon A, Foster C, Landry A, et al. The role of interleukin 1beta in the anti-adipogenic action of macrophages on human preadipocytes. J Endocrinol. 2013;217(2):197–206.CrossRefPubMed
13.
Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.CrossRefPubMedPubMedCentral
14.
Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–30.CrossRefPubMedPubMedCentral
15.
Jang MK, Son Y, Jung MH. ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity. Biochem Biophys Res Commun. 2013;431(3):421–7.CrossRefPubMed
16.
He Y, Lu L, Wei X, et al. The multimerization and secretion of adiponectin are regulated by TNF-alpha. Endocrine. 2016;51(3):456–68.CrossRefPubMed
17.
Kim JI, Huh JY, Sohn JH, et al. Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation. Mol Cell Biol. 2015;35(10):1686–99.CrossRefPubMedPubMedCentral
18.
Farnier C, Krief S, Blache M, et al. Adipocyte functions are modulated by cell size change: potential involvement of an integrin/ERK signalling pathway. Int J Obes Relat Metab Disord. 2003;27(10):1178–86.CrossRefPubMed
19.
Kosteli A, Sugaru E, Haemmerle G, et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest. 2010;120(10):3466–79.CrossRefPubMedPubMedCentral
20.
Girousse A, Tavernier G, Valle C, et al. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass. PLoS Biol. 2013;11(2):e1001485.CrossRefPubMedPubMedCentral
21.
Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444(7121):881–7.CrossRefPubMed
22.
Itani SI, Ruderman NB, Schmieder F, et al. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes. 2002;51(7):2005–11.CrossRefPubMed
23.
Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–41.CrossRefPubMed
24.
Mathieu P, Lemieux I, Despres JP. Obesity, inflammation, and cardiovascular risk. Clin Pharmacol Ther. 2010;87(4):407–16.CrossRefPubMed
25.
Clemente-Postigo M, Queipo-Ortuno MI, Fernandez-Garcia D, et al. Adipose tissue gene expression of factors related to lipid processing in obesity. PLoS One. 2011;6(9):e24783.CrossRefPubMedPubMedCentral
26.
Panarotto D, Remillard P, Bouffard L, et al. Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner. Eur J Clin Invest. 2002;32(2):84–92.CrossRefPubMed
27.
Kawakami M, Murase T, Ogawa H, et al. Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 cells. J Biochem. 1987;101(2):331–8.PubMed
28.
Greenberg AS, Nordan RP, McIntosh J, et al. Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. Cancer Res. 1992;52(15):4113–6.PubMed
29.
30.
Stefan N, Haring HU. The role of hepatokines in metabolism. Nat Rev Endocrinol. 2013;9(3):144–52.CrossRefPubMed
31.
Pal D, Dasgupta S, Kundu R, et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med. 2012;18(8):1279–85.CrossRefPubMed
32.
Heinrichsdorff J, Olefsky JM. Fetuin-A: the missing link in lipid-induced inflammation. Nat Med. 2012;18(8):1182–3.CrossRefPubMed
33.
Kloting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299(3):E506–15.CrossRefPubMed
34.
Karelis AD, Faraj M, Bastard JP, et al. The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab. 2005;90(7):4145–50.CrossRefPubMed
35.
Hyun YJ, Koh SJ, Chae JS, et al. Atherogenecity of LDL and unfavorable adipokine profile in metabolically obese, normal-weight woman. Obesity. 2008;16(4):784–9.CrossRefPubMed
36.••
Naukkarinen J, Heinonen S, Hakkarainen A, et al. Characterising metabolically healthy obesity in weight-discordant monozygotic twins. Diabetologia. 2014;57(1):167–76. Examines the underlying mechanisms of metabolic healthy using a unique subset of obesity-discordant monozygotic twin pairs separated into two subgroups based on the amount of liver fat. Increased liver fat in the obese twin resulted in dyslipidemia and adipose tissue dysfunction while normal levels of liver fat did not.
37.•
Fabbrini E, Yoshino J, Yoshino M, et al. Metabolically normal obese people are protected from adverse effects following weight gain. J Clin Invest. 2015;125(2):787–95. Weight-gain only leads to dyslipidemia and metabolic deterioration in obese subjects characterized by a high intrahepatic fat content. This suggests an important role of hepatic fat content in the development of dyslipidemia.
38.
Bohm A, Halama A, Meile T, et al. Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. PLoS One. 2014;9(4):e93148.CrossRefPubMedPubMedCentral
39.
Srdic B, Stokic E, Korac A, et al. Morphological characteristics of abdominal adipose tissue in normal-weight and obese women of different metabolic profiles. Exp Clin Endocrinol Diabetes. 2010;118(10):713–8.CrossRefPubMed
40.
Veilleux A, Caron-Jobin M, Noel S, et al. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes. 2011;60(5):1504–11.CrossRefPubMedPubMedCentral
41.
Moreno-Indias I, Oliva-Olivera W, Omiste A, et al. Adipose tissue infiltration in normal-weight subjects and its impact on metabolic function. Transl Res. 2016.
42.•
Fabbrini E, Cella M, McCartney SA, et al. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013;145(2):366–74 e1-3. The adipose tissue of unhealthy obese contains more CD4+ T-cells which produces IL17 and IL22 compared to healthy obese. These cytokines may cause metabolic dysfunction and contribute to the development of the unhealthy phenotype.
43.
Telle-Hansen VH, Halvorsen B, Dalen KT, et al. Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype. Genes Nutr. 2013;8(4):425–34.CrossRefPubMedPubMedCentral
44.
Lackey DE, Burk DH, Ali MR, et al. Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity. Am J Physiol Endocrinol Metab. 2014;306(3):E233–46.CrossRefPubMed
45.•
Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab. 2013;98(10):E1610–9. A large cross-sectional study utilizing five different definition of metabolic health, which suggests that inflammation is associated with the unhealthy phenotype in both obese and normal weight individuals regardless of how metabolic health is defined.
46.
Petersen KF, Dufour S, Savage DB, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A. 2007;104(31):12587–94.CrossRefPubMedPubMedCentral
47.
Perez-Martinez P, Alcala-Diaz JF, Delgado-Lista J, et al. Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis. Eur J Clin Invest. 2014;44(11):1053–64.CrossRefPubMed
48.
Rhee EJ, Lee MK, Kim JD, et al. Metabolic health is a more important determinant for diabetes development than simple obesity: a 4-year retrospective longitudinal study. PLoS One. 2014;9(5):e98369.CrossRefPubMedPubMedCentral
49.
Pujia A, Gazzaruso C, Ferro Y, et al. Individuals with metabolically healthy overweight/obesity have higher fat utilization than metabolically unhealthy individuals. Nutrients. 2016; 8(1).
50.
Katsuki A, Suematsu M, Gabazza EC, et al. Decreased high-molecular weight adiponectin-to-total adiponectin ratio in sera is associated with insulin resistance in Japanese metabolically obese, normal-weight men with normal glucose tolerance. Diabetes Care. 2006;29(10):2327–8.CrossRefPubMed
51.
Conus F, Allison DB, Rabasa-Lhoret R, et al. Metabolic and behavioral characteristics of metabolically obese but normal-weight women. J Clin Endocrinol Metab. 2004;89(10):5013–20.CrossRefPubMed
52.
Reinehr T, Karges B, Meissner T, et al. Fibroblast growth factor 21 and Fetuin-A in obese adolescents with and without type 2 diabetes. J Clin Endocrinol Metab. 2015;100(8):3004–10.CrossRefPubMed
53.
Badoud F, Lam KP, DiBattista A, et al. Serum and adipose tissue amino acid homeostasis in the metabolically healthy obese. J Proteome Res. 2014;13(7):3455–66.CrossRefPubMed
54.
Arner P, Bernard S, Salehpour M, et al. Dynamics of human adipose lipid turnover in health and metabolic disease. Nature. 2011;478(7367):110–3.CrossRefPubMedPubMedCentral
55.
Tynan GA, Hearnden CH, Oleszycka E, et al. Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1alpha-dependent inflammation. Diabetes. 2014;63(6):2037–50.CrossRefPubMed
56.
McLaughlin T, Lamendola C, Coghlan N, et al. Subcutaneous adipose cell size and distribution: relationship to insulin resistance and body fat. Obesity (Silver Spring). 2014;22(3):673–80.CrossRef
57.
Johannsen DL, Tchoukalova Y, Tam CS, et al. Effect of 8 weeks of overfeeding on ectopic fat deposition and insulin sensitivity: testing the “adipose tissue expandability” hypothesis. Diabetes Care. 2014;37(10):2789–97.CrossRefPubMedPubMedCentral
58.
Esser N, L’Homme L, De Roover A, et al. Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue. Diabetologia. 2013;56(11):2487–97.CrossRefPubMed
59.
60.
Ilan Y, Maron R, Tukpah AM, et al. Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci U S A. 2010;107(21):9765–70.CrossRefPubMedPubMedCentral
61.
Kim JY, van de Wall E, Laplante M, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621–37.CrossRefPubMedPubMedCentral
62.
Kusminski CM, Holland WL, Sun K, et al. MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity. Nat Med. 2012;18(10):1539–49.CrossRefPubMedPubMedCentral
63.
Saponaro C, Gaggini M, Carli F, et al. The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients. 2015;7(11):9453–74.CrossRefPubMedPubMedCentral
64.
65.
Perry RJ, Samuel VT, Petersen KF, et al. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature. 2014;510(7503):84–91.CrossRefPubMedPubMedCentral
66.
Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836–46.CrossRefPubMed
67.
Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol. 2013;10(11):656–65.CrossRefPubMed
68.
Fabbrini E, Magkos F, Mohammed BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A. 2009;106(36):15430–5.CrossRefPubMedPubMedCentral
69.
Fabbrini E, Mohammed BS, Magkos F, et al. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology. 2008;134(2):424–31.CrossRefPubMed
70.
Lucero D, Zago V, Lopez GI, et al. Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome? Clin Chim Acta. 2011;412(7-8):587–92.CrossRefPubMed
71.
Berti L, Irmler M, Zdichavsky M, et al. Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes. Mol Metab. 2015;4(7):519–27.CrossRefPubMedPubMedCentral
72.
Oliveros E, Somers VK, Sochor O, et al. The concept of normal weight obesity. Prog Cardiovasc Dis. 2014;56(4):426–33.CrossRefPubMed
73.
Samocha-Bonet D, Dixit VD, Kahn CR, et al. Metabolically healthy and unhealthy obese—the 2013 Stock Conference report. Obes Rev. 2014;15(9):697–708.CrossRefPubMedPubMedCentral
74.
Korenblat KM, Fabbrini E, Mohammed BS, et al. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology. 2008;134(5):1369–75.CrossRefPubMedPubMedCentral
75.
Hojland Ipsen D, Tveden-Nyborg P, Lykkesfeldt J. Normal weight dyslipidemia: is it all about the liver? Obesity (Silver Spring). 2016;24(3):556–67.CrossRef
76.
Tessari P, Coracina A, Cosma A, et al. Hepatic lipid metabolism and non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2009;19(4):291–302.CrossRefPubMed
Metadaten
Titel
Dyslipidemia: Obese or Not Obese—That Is Not the Question
verfasst von
David H. Ipsen
Pernille Tveden-Nyborg
Jens Lykkesfeldt
Publikationsdatum
29.09.2016
Verlag
Springer US
Erschienen in
Current Obesity Reports / Ausgabe 4/2016
Elektronische ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-016-0232-9

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