Background & Aims
Methods
Results
Conclusions
Graphical abstract

Keywords
Abbreviations used in this paper:
CHO (carbohydrate), DNL (de novo lipogenesis), eWAT (epididymal white adipose tissue), MHO (metabolically healthy obese), MUO (metabolically unhealthy obese), NK (natural killer), TG (triglyceride)- Ng M.
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- Thomson B.
- Graetz N.
- Margono C.
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- Biryukov S.
- Abbafati C.
- Abera S.F.
- Abraham J.P.
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- Achoki T.
- AlBuhairan F.S.
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- Ali M.K.
- Ali R.
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- Ammar W.
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- Blore J.
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- Hernandez L.
- Husseini A.
- Idrisov B.T.
- Ikeda N.
- Islami F.
- Jahangir E.
- Jassal S.K.
- Jee S.H.
- Jeffreys M.
- Jonas J.B.
- Kabagambe E.K.
- Khalifa S.E.
- Kengne A.P.
- Khader Y.S.
- Khang Y.H.
- Kim D.
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- Kwan G.
- Lai T.
- Leinsalu M.
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- Liang X.
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- Naghavi M.
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- Nelson E.L.
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- Shiri R.
- Shiue I.
- Singh G.M.
- Singh J.A.
- Skirbekk V.
- Stapelberg N.J.
- Sturua L.
- Sykes B.L.
- Tobias M.
- Tran B.X.
- Trasande L.
- Toyoshima H.
- van de Vijver S.
- Vasankari T.J.
- Veerman J.L.
- Velasquez-Melendez G.
- Vlassov V.V.
- Vollset S.E.
- Vos T.
- Wang C.
- Wang X.
- Weiderpass E.
- Werdecker A.
- Wright J.L.
- Yang Y.C.
- Yatsuya H.
- Yoon J.
- Yoon S.J.
- Zhao Y.
- Zhou M.
- Zhu S.
- Lopez A.D.
- Murray C.J.
- Gakidou E.
- Stanhope K.L.
- Schwarz J.M.
- Keim N.L.
- Griffen S.C.
- Bremer A.A.
- Graham J.L.
- Hatcher B.
- Cox C.L.
- Dyachenko A.
- Zhang W.
- McGahan J.P.
- Seibert A.
- Krauss R.M.
- Chiu S.
- Schaefer E.J.
- Ai M.
- Otokozawa S.
- Nakajima K.
- Nakano T.
- Beysen C.
- Hellerstein M.K.
- Berglund L.
- Havel P.J.
- Chiu S.
- Sievenpiper J.L.
- de Souza R.J.
- Cozma A.I.
- Mirrahimi A.
- Carleton A.J.
- Ha V.
- Di Buono M.
- Jenkins A.L.
- Leiter L.A.
- Wolever T.M.
- Don-Wauchope A.C.
- Beyene J.
- Kendall C.W.
- Jenkins D.J.
- Teng K.T.
- Chang L.F.
- Vethakkan S.R.
- Nesaretnam K.
- Sanders T.A.
Methods
Animals and Diets
Nutrient (g/kg) | Chow | Sucrose palmitate | Starch palmitate | Sucrose oleate | Starch oleate | Western diet | |
---|---|---|---|---|---|---|---|
Amino acids | L-Alanine | 11.9 | 4.5 | 4.5 | 4.5 | 4.5 | 5.1 |
L-Arginine, fb | 12.9 | 6.3 | 6.3 | 6.3 | 6.3 | 6.4 | |
L-Aspartic acid | 21.9 | 11.3 | 11.3 | 11.3 | 11.3 | 11.7 | |
L-Cystine | 3.6 | 3.7 | 3.7 | 3.7 | 3.7 | 0.5 | |
L-Glutamic acid | 41.8 | 36.2 | 36.2 | 36.2 | 36.2 | 35.5 | |
Glycine | 9.7 | 3.1 | 3.1 | 3.1 | 3.1 | 3.1 | |
L-Histidine, f b | 5.3 | 4.5 | 4.5 | 4.5 | 4.5 | 4.9 | |
L-Isoleucine | 8.6 | 8.4 | 8.4 | 8.4 | 8.4 | 9.8 | |
L-Leucine | 15.7 | 15.3 | 15.3 | 15.3 | 15.3 | 15.6 | |
L-Lysine-HCl | 11.8 | 16.1 | 16.1 | 16.1 | 16.1 | 13.7 | |
L-Methionine | 6.2 | 2.0 | 2.0 | 2.0 | 2.0 | 10.5 | |
L-Phenylalanine | 9.1 | 8.7 | 8.7 | 8.7 | 8.7 | 8.6 | |
L-Proline | 13.1 | 20.4 | 20.4 | 20.4 | 20.4 | 17.6 | |
L-Serine | 9.8 | 9.4 | 9.4 | 9.4 | 9.4 | 9.8 | |
L-Threonine | 7.8 | 6.6 | 6.6 | 6.6 | 6.6 | 7.4 | |
L-Tryptophan | 2.4 | 2.1 | 2.1 | 2.1 | 2.1 | 2.0 | |
L-Tyrosine | 6.0 | 9.2 | 9.2 | 9.2 | 9.2 | 9.0 | |
L-Valine | 9.7 | 9.9 | 9.9 | 9.9 | 9.9 | 11.7 | |
Choline chloride | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | |
SUBTOTAL | 209.3 | 179.7 | 179.7 | 179.7 | 179.7 | 184.9 | |
Carbohydrate | Cornstarch | 286 | — | 472.9 | — | 472.9 | 150.0 |
Cellulose | 216 | 80.0 | 80.0 | 80.0 | 80.0 | 50.0 | |
Fructose | 2.4 | — | — | — | — | — | |
Glucose | 1.9 | — | — | — | — | — | |
Lactose | 13.4 | — | — | — | — | — | |
Sucrose | 32.4 | 456.9 | — | 456.9 | — | 341.5 | |
SUBTOTAL | 552.1 | 536.9 | 552.9 | 536.9 | 552.9 | 541.5 | |
Fat | Saturated fats | 7.8 | 220.6 | 205.4 | 19.4 | 18.1 | 131.0 |
Monounsaturated fats | 9.7 | 1.4 | 1.3 | 187.1 | 174.2 | 57.9 | |
Polyunsaturated fats | 32.5 | 9.0 | 8.4 | 24.5 | 22.8 | 21.6 | |
Cholesterol | 0.1 | — | — | — | — | 1.5 | |
Main source | Soybean oil | Tripalmitin | Tripalmitin | High-oleic sunflower oil | High-oleic sunflower oil | Anhydrous milk fat | |
SUBTOTAL | 50.1 | 231.0 | 215.1 | 231.0 | 215.0 | 212.0 | |
% kcal | Protein | 24.5 | 14.6 | 15.4 | 14.6 | 15.4 | 15.2 |
CHO | 62.3 | 42.7 | 42.5 | 42.7 | 42.5 | 42.7 | |
Fat | 13.1 | 42.7 | 42.1 | 42.7 | 42.1 | 42.0 |
Serum Chemistries
Glucose Tolerance Test
- Pierce A.A.
- Duwaerts C.C.
- Soon R.K.
- Siao K.
- Grenert J.P.
- Fitch M.
- Hellerstein M.K.
- Beysen C.
- Turner S.M.
- Maher J.J.
Measurement of Hepatic Lipids
Histology and Immunohistochemistry
Measurement of Adipose Tissue Gene Expression
Measurement of De Novo Lipogenesis
Adipose Tissue Lipolysis
Stromal Vascular Cell Isolation and Flow Cytometry
Statistical Analysis
Data
Results
A Starch-Oleate Diet Induces More Hepatic Steatosis Than Do Isocaloric Diets Featuring Other Nutrients


Steatosis (0–3) | Ballooning (0–3) | Inflammation (0–2) | ALT (IU/L) | Insulin (ng/mL) | |
---|---|---|---|---|---|
Chow | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.1 | 47 ± 3 | 0.52 ± 0.08 |
Suc Pal | 1.0 ± 0.3 | 0.0 ± 0.1 | 0.0 ± 0.1 | 61 ± 4 | 0.68 ± 0.13 |
St Pal | 1.0 ± 0.2 | 0.0 ± 0.2 | 0.0 ± 0.0 | 68 ± 4 | 1.78 ± 0.24 |
Suc Ol | 1.0 ± 0.2 | 1.0 ± 0.3 | 0.0 ± 0.1 | 58 ± 5 | 0.87 ± 0.37 |
St Ol | 3.0 ± 0.2 | 2.0 ± 0.2 | 0.0 ± 0.2 | 77 ± 4 | 1.83 ± 1.2 |
Starch-Oleate Feeding Increases Hepatic DNL and Incorporation of Fat From Adipose Tissue

Starch-Oleate Feeding Induces Histologic and Functional Changes in eWAT as It Induces Hepatic Steatosis

eWAT Necrosis (0–3) | |
---|---|
Chow | 0.9 ± 0.2 |
Suc Pal | 0.8 ± 0.3 |
St Pal | 1.2 ± 0.2 |
Suc Ol | 1.1 ± 0.2 |
St Ol | 2.0 ± 0.2 |



Effects of Starch-Oleate Feeding on Liver and Adipose Tissue Phenocopy Those of the Western Diet

Discussion
- Kouvari M.
- Notara V.
- Panagiotakos D.B.
- Michalopoulou M.
- Vassileiou N.
- Papataxiarchis E.
- Tzanoglou D.
- Mantas Y.
- Kogias Y.
- Stravopodis P.
- Papanagnou G.
- Zombolos S.
- Pitsavos C.
- Jebb S.A.
- Lovegrove J.A.
- Griffin B.A.
- Frost G.S.
- Moore C.S.
- Chatfield M.D.
- Bluck L.J.
- Williams C.M.
- Sanders T.A.
- Lynch L.
- Michelet X.
- Zhang S.
- Brennan P.J.
- Moseman A.
- Lester C.
- Besra G.
- Vomhof-Dekrey E.E.
- Tighe M.
- Koay H.F.
- Godfrey D.I.
- Leadbetter E.A.
- Sant'Angelo D.B.
- von Andrian U.
- Brenner M.B.
- Klein-Wieringa I.R.
- Andersen S.N.
- Kwekkeboom J.C.
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- Huizinga T.W.
- Kloppenburg M.
- Toes R.E.
- Ioan-Facsinay A.
- Pierce A.A.
- Duwaerts C.C.
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- Grenert J.P.
- Fitch M.
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- Beysen C.
- Turner S.M.
- Maher J.J.
- Asgharpour A.
- Cazanave S.C.
- Pacana T.
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- Banini B.A.
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- Hoshida Y.
- Koduru S.V.
- Contaifer Jr., D.
- Warncke U.O.
- Wijesinghe D.S.
- Sanyal A.J.
Acknowledgments
Supplementary Material
- Supplementary Table 1
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Article info
Publication history
Footnotes
Author contributions Study design (CCD, JJM); data acquisition (CCD, AMA, KS, CH, CB, MF, AG, JPG, SJC); data analysis and interpretation (CCD, AMA, CB, MF, AG, JB, JJM); manuscript preparation (CCD, JJM); and critical revision of manuscript (JLB).
Conflicts of interest The authors declare no conflicts.
Funding This study was supported by R01 DK068450 (J.J.M.), T32 DK068414 (C.C.D., A.M.A.), the UCSF Liver Center (P30 DK026743), and the Vanderbilt Mouse Metabolic Phenotyping Center (U24 DK059637).
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