Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice

被引:35
作者
den Hartigh, Laura J. [1 ]
Wang, Shari [1 ]
Goodspeed, Leela [1 ]
Wietecha, Tomasz [2 ]
Houston, Barbara [1 ]
Omer, Mohamed [1 ]
Ogimoto, Kayoko [1 ]
Subramanian, Savitha [1 ]
Gowda, G. A. Nagana [3 ]
O'Brien, Kevin D. [2 ]
Kaiyala, Karl J. [4 ]
Morton, Gregory J. [1 ]
Chait, Alan [1 ]
机构
[1] Univ Washington, Dept Med, Metab, Seattle, WA 98105 USA
[2] Univ Washington, Dept Med, Cardiol, Seattle, WA USA
[3] Univ Washington, Dept Anesthesiol & Pain Med, Northwest Metabol Res Ctr, Seattle, WA 98195 USA
[4] Univ Washington, Dept Oral Hlth Sci, Seattle, WA 98195 USA
来源
PLOS ONE | 2017年 / 12卷 / 02期
关键词
CONJUGATED LINOLEIC-ACID; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; BODY-COMPOSITION; RISK MARKERS; OBESE MEN; BROWN-FAT; SUPPLEMENTATION; TRANS-10; INFLAMMATION;
D O I
10.1371/journal.pone.0172912
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Widely used as a weight loss supplement, trans-10, cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. Objective We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. Methods Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured. Results By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation. Conclusions These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.
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页数:25
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共 65 条
[21]   t10,c12 Conjugated Linoleic Acid Upregulates Hepatic De Novo Lipogenesis and Triglyceride Synthesis via mTOR Pathway Activation [J].
Gwang-woong, Go ;
Oh, Sangnam ;
Park, Miri ;
Gang, Gyoungok ;
McLean, Danielle ;
Yang, Han-sul ;
Song, Min-Ho ;
Kim, Younghoon .
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2013, 23 (11) :1569-1576
[22]   Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid to obese-prone rats impairs glucose and insulin tolerance [J].
Hamilton, Melissa ;
Hopkins, Loren E. ;
AlZahal, Ousama ;
MacDonald, Tara L. ;
Cervone, Daniel T. ;
Wright, David C. ;
McBride, Brian W. ;
Dyck, David J. .
LIPIDS IN HEALTH AND DISEASE, 2015, 14
[23]   Role of PPARγ in regulating adipocyte differentiation and insulin-responsive glucose uptake [J].
Hamm, JK ;
El Jack, AK ;
Pilch, PF ;
Farmer, SR .
THE METABOLIC SYNDROME X: CONVERGENCE OF INSULIN RESISTANCE, GLUCOSE INTOLERANCE, HYPERTENSION, OBESITY, AND DYSLIPIDEMIAS-SEARCHING FOR THE UNDERLYING DEFECTS, 1999, 892 :134-145
[24]   The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women [J].
Harvie, Michelle ;
Wright, Claire ;
Pegington, Mary ;
McMullan, Debbie ;
Mitchell, Ellen ;
Martin, Bronwen ;
Cutler, Roy G. ;
Evans, Gareth ;
Whiteside, Sigrid ;
Maudsley, Stuart ;
Camandola, Simonetta ;
Wang, Rui ;
Carlson, Olga D. ;
Egan, Josephine M. ;
Mattson, Mark P. ;
Howell, Anthony .
BRITISH JOURNAL OF NUTRITION, 2013, 110 (08) :1534-1547
[25]   PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy [J].
Hegele, RA ;
Cao, HN ;
Frankowski, C ;
Mathews, ST ;
Leff, T .
DIABETES, 2002, 51 (12) :3586-3590
[26]   Novel Markers to Delineate Murine M1 and M2 Macrophages [J].
Jablonski, Kyle A. ;
Amici, Stephanie A. ;
Webb, Lindsay M. ;
Ruiz-Rosado, Juan de Dios ;
Popovich, Phillip G. ;
Partida-Sanchez, Santiago ;
Guerau-de-Arellano, Mireia .
PLOS ONE, 2015, 10 (12)
[27]   Hepatic glucose and lipid metabolism [J].
Jones, John G. .
DIABETOLOGIA, 2016, 59 (06) :1098-1103
[28]   Leptin Signaling Is Required for Adaptive Changes in Food Intake, but Not Energy Expenditure, in Response to Different Thermal Conditions [J].
Kaiyala, Karl J. ;
Ogimoto, Kayoko ;
Nelson, Jarrell T. ;
Schwartz, Michael W. ;
Morton, Gregory J. .
PLOS ONE, 2015, 10 (03)
[29]   Toward a More Complete (and Less Controversial) Understanding of Energy Expenditure and Its Role in Obesity Pathogenesis [J].
Kaiyala, Karl J. ;
Schwartz, Michael W. .
DIABETES, 2011, 60 (01) :17-23
[30]   The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects [J].
Kamphuis, MMJW ;
Lejeune, MPGM ;
Saris, WHM ;
Westerterp-Plantenga, MS .
INTERNATIONAL JOURNAL OF OBESITY, 2003, 27 (07) :840-847