Fatty Acid Synthesis De Novo in Adipose Tissue from Obese Subjects on a Hypercaloric High-Carbohydrate Diet

Metabolic and enzymic changes were measured in meal-trained rats fed on high-carbohydrate diet. Rates of hepatic fatty acid synthesis are probably greater than rates of gluconeogenesis throughout the 24 h day provided that animals are fed. The daily enhancement of fatty acid synthesis on meal feeding coincided with the maximum activation of hepatic pyruvate kinase. Maximum activation of this enzyme was reflected in increased total catalytic activity (Vmax.), increased activity at 0.5 MM-phosphoenolpyruvate (V0.5), decreased Vmax./V0.5 ratio and a decrease in co-operativity of phosphoenolpyruvate binding as measured by the Hill coefficient (h). The latter changes are consistent with a decrease in enzyme phosphorylation during activation of the enzyme. To estimate changes in enzyme protein, quantitative enzyme precipitation with rabbit antisera was used. Giving a high-carbohydrate diet to meal-trained animals induced enzyme synthesis within a few hours. Adaptations in diet that enhanced fatty acid synthesis (chow to high carbohydrate; starved to high carbohydrate) led to an increased steady-state concentration of pyruvate kinase protein. An approximate estimate of the half-life of hepatic pyruvate kinase was 56 h. Whenever pyruvate kinase specific activity was measured in liver tissue extracts it was always considerably less (20–100 mumol/min per mg of protein, depending on dietary status) than the specific activity of pure pyruvate kinase (200 mumol/min per mg of protein). Antigenically active, catalytically inactive protein was removed during enzyme purification from cytosol at the stage of (NH4)2SO4 fractionation. The fraction precipitated by 30–45%-satd. (NH4)2SO4 was enzymically active, antigenically reacting protein was identified in the remaining (NH4)2SO4 fractions (0–30%- and 45–85%-satd.) and this contained no enzyme activity. These may correspond to inactive proteolytic fragments of pyruvate kinase. The rate-determining step in adjusting enzyme concentration seems to be proteolysis.

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Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.

Journal of Clinical Investigation ◽

10.1172/jci118645 ◽

1996 ◽

Vol 97 (9) ◽

pp. 2081-2091 ◽

Cited By ~ 241

Author(s):

L C Hudgins ◽

M Hellerstein ◽

C Seidman ◽

R Neese ◽

J Diakun ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

High Carbohydrate Diet ◽

Low Fat ◽

Carbohydrate Diet ◽

High Carbohydrate

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Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.253.6.e664 ◽

1987 ◽

Vol 253 (6) ◽

pp. E664-E669 ◽

Cited By ~ 5

Author(s):

C. Chascione ◽

D. H. Elwyn ◽

M. Davila ◽

K. M. Gil ◽

J. Askanazi ◽

...

Keyword(s):

Adipose Tissue ◽

De Novo ◽

Acid Synthesis ◽

De Novo Lipogenesis ◽

Whole Body ◽

High Intake ◽

Carbohydrate Diet ◽

Triglyceride Synthesis ◽

High Carbohydrate

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

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Alternative pathway of free fatty acid uptake from phospholipids and upregulation of de novo fatty acid synthesis in lipoprotein lipase-deficient murine adipose tissue

Atherosclerosis Supplements ◽

10.1016/s1567-5688(02)80369-5 ◽

2002 ◽

Vol 3 (2) ◽

pp. 145

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Lipoprotein Lipase ◽

Fatty Acid Synthesis ◽

De Novo ◽

Alternative Pathway ◽

Acid Synthesis ◽

Fatty Acid Uptake ◽

Acid Uptake

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Downregulation of de Novo Fatty Acid Synthesis in Subcutaneous Adipose Tissue of Moderately Obese Women

International Journal of Molecular Sciences ◽

10.3390/ijms161226206 ◽

2015 ◽

Vol 16 (12) ◽

pp. 29911-29922 ◽

Cited By ~ 8

Author(s):

Esther Guiu-Jurado ◽

Teresa Auguet ◽

Alba Berlanga ◽

Gemma Aragonès ◽

Carmen Aguilar ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Fatty Acid Synthesis ◽

Subcutaneous Adipose Tissue ◽

De Novo ◽

Acid Synthesis ◽

Obese Women ◽

Subcutaneous Adipose

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Effects of pregnancy and ovarian steroids on fatty acid synthesis and uptake in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.1.r153 ◽

1991 ◽

Vol 260 (1) ◽

pp. R153-R158 ◽

Cited By ~ 1

Author(s):

A. J. Bhatia ◽

G. N. Wade

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

White Adipose Tissue ◽

Fatty Acid Synthesis ◽

De Novo ◽

Acid Synthesis ◽

De Novo Lipogenesis ◽

Ovarian Steroids ◽

Syrian Hamsters

The effects of pregnancy and ovarian steroids on the in vivo distribution of newly synthesized fatty acids (incorporation of tritium from 3H2O into fatty acid) in Syrian hamsters (Mesocricetus auratus) were examined. During late, but not early, gestation hamsters had reduced levels of newly synthesized fatty acids in heart, liver, uterus, and white adipose tissues (parametrial and inguinal fat pads). Treatment of ovariectomized hamsters with estradiol + progesterone significantly decreased fatty acid synthesis-uptake in heart, liver, and inguinal white adipose tissue. Treatment with either estradiol or progesterone alone was without significant effect in any tissue. Pretreatment of hamsters with Triton WR-1339 (tyloxapol), an inhibitor of lipoprotein lipase activity and tissue triglyceride uptake, abolished the effects of estradiol + progesterone in white adipose tissue and heart but not in liver. Thus hamsters lose body fat during pregnancy in part because of decreased de novo lipogenesis. The effect of pregnancy on lipogenesis is mimicked by treatment with estradiol + progesterone but not by either hormone alone. Furthermore, it appears that the liver is the principal site of estradiol + progesterone action on lipogenesis in Syrian hamsters.

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Developmental changes in fatty acid synthesis in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice

Biochemical Journal ◽

10.1042/bj2120393 ◽

1983 ◽

Vol 212 (2) ◽

pp. 393-398 ◽

Cited By ~ 33

Author(s):

S W Mercer ◽

P Trayhurn

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Obese Mice ◽

Carbohydrate Diet ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose

Fatty acid synthesis was measured in vivo with 3H2O in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice. At 26 days of age, before the development of hyperphagia, synthesis in brown adipose tissue was higher in the obese than in the lean mice; synthesis was also elevated in the liver, white adipose tissue and carcass of the obese mice. At 8 weeks of age, when hyperphagia was well established, synthesis remained elevated in all tissues of the obese mice, with the exception of brown adipose tissue. Elevated synthesis rates were not apparent in brown adipose tissue of the obese mice at 14 days of age, nor at 35 days of age. These results demonstrate that brown adipose tissue in ob/ob mice has a transitory hyperlipogenesis at, and just after, weaning on to a low-fat/high-carbohydrate diet. Once hyperphagia has developed, by week 5 of life, brown adipose tissue is the only major lipogenic tissue in the obese mice not to exhibit elevated rates of fatty acid synthesis; this suggests that insulin resistance develops much more rapidly in brown adipose tissue than in other lipogenic tissues of the ob/ob mouse.

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Influence of diet on the modeling of adipose tissue triglycerides during growth

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00128.2003 ◽

2003 ◽

Vol 285 (4) ◽

pp. E917-E925 ◽

Cited By ~ 62

Author(s):

Daniel Z. Brunengraber ◽

Brendan J. McCabe ◽

Takhar Kasumov ◽

James C. Alexander ◽

Visvanathan Chandramouli ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

De Novo ◽

High Carbohydrate Diet ◽

De Novo Lipogenesis ◽

High Fat ◽

Carbohydrate Diet ◽

Triglyceride Synthesis ◽

High Carbohydrate ◽

Synthesis And Degradation

We have studied the accretion of lipids in growing mice. We measured the rates of synthesis and degradation of triglycerides in epididymal fat pads of mice maintained for 44 days on a low-fat, high-carbohydrate diet ( I) or a high-fat, lowcarbohydrate diet ( II). 2H2O was added to the drinking water for 14 days. Rates of incorporation/washout of 2H to/from C1 of triglyceride-glycerol showed that triglyceride synthesis was greater than triglyceride degradation (net triglyceride balance was ∼2.5 times greater in II than in I). The data also show that the contribution of de novo lipogenesis to triglyceride-bound palmitate was ∼3 times greater in I than in II. This was consistent with a greater relative intake of carbohydrate in I vs. II. The rates of incorporation and washout of newly synthesized (2H-labeled) palmitate into and from triglycerides were also measured. Those data suggested a remodeling of triglyceride-bound fatty acids. On measuring the profile of triglyceride-bound fatty acids, we observed a decrease in the relative abundance of triglyceride-bound palmitate and stearate and an increase in triglyceride-bound oleate and linoleate. This was observed in I and II. In summary, diet substantially affects the deposition and modeling of triglycerides in adipose tissue during growth. 2H2O can be used to examine the mechanisms responsible for the accumulation of triglycerides, e.g., factors that affect 1) triglyceride synthesis and degradation and 2) the source of fatty acids that are used in esterification.

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