Markedly Blunted Metabolic Effects of Fructose in Healthy Young Female Subjects Compared With Male Subjects

Couchepin, Caroline; Lê, Kim-Anne; Bortolotti, M.; Encarnaçao, Joana Amarante da; Oboni, Jean-Baptiste; Tran, Christel; Schneiter, Philippe; Tappy, Luc

doi:10.2337/dc07-2001

Cited by 89 publications

(90 citation statements)

References 12 publications

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“…Thus, a lesser increase in plasma TAG after fructose ingestion is observed in pre-menopausal women, but not in post-menopausal women (5) . In rodents, sex differences in metabolic responses to fructose can be eliminated by oophorectomy and restored by oestrogen substitution (6,7) . Our observation points to a dual effect of oestrogens, which stimulate adipose tissue lipolysis while decreasing hepatic DNL.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load

et al. 2010

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The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with 13 C 6 fructose. Incorporation of 13 C into breath CO 2 , plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After 13 C fructose ingestion, 44·0 (SD 3·2) % of labelled carbons were recovered in plasma glucose in males v. 41·9 (SD 2·3) % in females (NS), and 42·9 (SD 3·7) % of labelled carbons were recovered in breath CO 2 in males v. 43·0 (SD 4·5) % in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for 13 C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P,0·05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16·4 (SD 5·2), P, 0·05), but it was not suppressed in females (2 1·3 (SD 4·7) %). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation. De novo lipogenesis: VLDL TAG: Endogenous glucose productionThe metabolic effects of a high-fructose diet have been widely studied in both animals and human subjects (1) . High-fructose diet is associated with the development of at least two features of the metabolic syndrome, i.e. insulin resistance and increased plasma VLDL TAG. The latter may in turn be associated with an increased production of small, dense LDL particle with high atherogenic potential (2,3) . It has been reported by several authors that a high-fructose diet increases plasma TAG less and does not reduce insulin sensitivity in both pre-menopausal women and female rodents compared with males (4 -11) . This may be due to a sex-specific difference in either fructose metabolism or adaptations to chronic fructose overfeeding. To our knowledge, whether the metabolism of an acute fructose load differs in females and males has not been specifically assessed. Fructose disposal relies mainly on the stimulation of carbohydrate oxidation (fructose oxidation in splanchnic organs and indirect oxidation of glucose and lactate synthesised from the fructose), gluconeogenesis, hepatic glycogen storage and hepatic de novo lipogenesis (DNL). The latter, although a quantitatively minor pathway for fructose disposal, may be closely linked to hepatic VLDL TAG production and synthesis of intra-hepatic lipids. Therefore, we hypothesised that fructose-induced stimulation of DNL may be blunted in pre-menopausal women.To evaluate this hypothesis, we compared the metabolic fate of i...

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Section: Discussionmentioning

confidence: 99%

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load

et al. 2010

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“…Based on animal experiments, an increased VLDL-triacylglycerol secretion is also likely to be involved [28]. The increase in plasma triglyceride induced by fructose is significantly blunted in females, which suggests that female sex hormones may exert a protective effect [29,30]. In humans, a high-fructose, hypercaloric diet leads to ectopic fat deposition in liver cells and skeletal muscle in humans already after a 1-wk period [31].…”

Section: What Are the Mechanisms Responsible For Fructose-induced Metmentioning

confidence: 99%

Fructose and metabolic diseases: New findings, new questions

et al. 2010

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There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.Pure, white, and deadly: the dark side of sugar was suspected many years ago, when an association between sugar consumption and coronary heart diseases was recognized and emphasized by John Yudkin [1]. Sugar, a natural sweetener obtained from either sugar cane or beets, is a disaccharide composed of one glucose molecule linked through an α1-4 glycoside bond to a fructose molecule. Fructose, besides contributing to half the total content of sugar, can also be found as a hexose in fruits and honey. More recently, sweeteners started to be produced from corn through starch isolation and hydrolysis to glucose, followed by enzymatic isomerization of part of the glucose into fructose [2,3]. The resulting mixture, known as high-fructose corn syrup (HFCS), has several industrial advantages over sugar, the most important being its low price, and has progressively replaced sugar consumption in North America over the past 30 years.Fructose metabolism has been reviewed extensively elsewhere [4][5][6] and will be only briefly outlined here. In the gut, fructose is transported by specific transporters, GLUT5 [7,8]. In some subjects, fructose absorption is quantitatively limited, and some malabsorption occurs when lar...

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“…These responses in lipids are seen primarily in men, with smaller or limited responses seen in women. 33,34 Fructose increases thermogenesis and blood pressure more than glucose, 35,36 but both have this effect. When a 75 g oral load of glucose or fructose was given to 17 volunteers, fructose stimulated oxygen consumption more than glucose but produced a much smaller stimulation of insulin.…”

Section: Short-term Effects Of Fructose On Human Metabolismmentioning

confidence: 99%

Fructose: Pure, White, and Deadly? Fructose, by Any other Name, is a Health Hazard

Bray

2010

J Diabetes Sci Technol

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The worldwide consumption of sucrose, and thus fructose, has risen logarithmically since 1800. Many concerns about the health hazards of calorie-sweetened beverages, including soft drinks and fruit drinks and the fructose they provide, have been voiced over the past 10 years. These concerns are related to higher energy intake, risk of obesity, risk of diabetes, risk of cardiovascular disease, risk of gout in men, and risk of metabolic syndrome. Fructose appears to be responsible for most of the metabolic risks, including high production of lipids, increased thermogenesis, and higher blood pressure associated with sugar or high fructose corn syrup. Some claim that sugar is natural, but natural does not assure safety.

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Markedly Blunted Metabolic Effects of Fructose in Healthy Young Female Subjects Compared With Male Subjects

Cited by 89 publications

References 12 publications

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load

Fructose and metabolic diseases: New findings, new questions

Fructose: Pure, White, and Deadly? Fructose, by Any other Name, is a Health Hazard

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