Lipid metabolism in women

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory alpha adrenergic receptors in abdominal regions and greater alpha adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer alpha adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.     

Visceral fat and insulin resistance--causative or correlative?

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.     

Effects of age, diet and lactation on lipogenesis in rat adipose, liver and mammary tissues

Four diets varying in safflower oil content from zero to 20% were used in a study of interactions among diet and physiological state. Increasing fat in the diet did not alter food intakes but decreased digestibility coefficients. Increasing safflower oil intake did not alter milk fat content in lactating rats but increased relative amounts of unsaturated fatty acids in milk fat. In liver and perirenal adipose tissues from young male and non-lactating female rats, low fat diets increased rates of lipogenesis from glucose in vitro and specific activities of enzymes whose functions are closely associated with lipogenesis. This adaptive hyperlipogenic response was not evident or was less prominent in aged or lactating rats. In the case of lactating rats it appears that lactation produces a marked reduction in adipose lipogenesis when low fat diets are fed. Reduced glyceride glycerol synthesis in lactating as compared to non-lactating rat adipose coupled with reduced fatty acid synthesis and in increased lipolysis indicated a shift in adipose function in the direction of increased fat mobilization as would be supportive of lactation. Only minor diet effects upon mammary enzyme patterns and rates of in vitro lipogenesis were observed.     

Non-esterified fatty acid and glycerol kinetics and fatty acid re-esterification in goats during early lactation

Non-esterified fatty acid (NEFA) and glycerol kinetics were studied in lactating goats to gain insight into the mechanisms by which animals in early lactation can initially mobilize and later replenish body fat reserves. Kinetic measurements were made at days 10, 38 and 76 post-partum in ten multiparous lactating does. Plasma NEFA concentrations and NEFA entry rate decreased as lactation advanced, being significantly higher at day 10 than at either days 38 or 76 of lactation. Both plasma NEFA concentrations and NEFA entry rate were negatively correlated with calculated energy balance. In contrast, glycerol entry rate was significantly higher at day 76 than at day 10 of lactation and was positively related to both calculated energy intake and energy balance. Apparent intracellular fatty acid re-esterification was lower at day 10 than at later stages of lactation and was positively related to calculated energy balance. It is suggested that during early lactation, substantial shifts in adipose tissue fat reserves can occur via altering rates of fatty acid re-esterification and de novo lipogenesis, without major changes in the rate of lipolysis.     

Dietary induction of rat liver fatty acid binding protein

Fatty acid binding protein (FABP) present in liver, myocardium, intestine and adipose tissue is involved in the intercellular metabolism of long chain fatty acids. It is known that lipogenic enzymes respond to dietary manipulation, so in the present study we investigated the possible changes induced by high carbohydrate and high fat diets on FABP. The binding activity for [¹⁴C] palmitoyl CoA to FABP fraction was 120% and 148% of control in response to high carbohydrate and high fat diets respectively. These changes in FABP concentration indicate involvement of this protein in the regulation of fatty acid metabolism within the cell. fatty acid binding protein, metabolism     

The impact of body composition on the regulation of lipolysis during short-term fasting.

Lipolytic rates were determined in normal-weight young adult (low body fat), normal-weight elderly (moderate body fat), and obese young adult (high body fat) subjects after an overnight (12-15 hr) and short-term (60-87 hr) fasting period. A simultaneous infusion of [1-13C] palmitate acid and [2H5]glycerol was used to measure the inflow of palmitate and glycerol into the bloodstream, and H2 18O dilution was used to measure body composition. The amount of body fat differed between the young adult (11 kg), elderly (23 kg) and obese (49 kg) subjects. Total lean body mass was similar in the normal-weight young adult (60 kg) and obese (63 kg) groups, but was lower in the elderly (46 kg). Lipolytic rates per unit of fat mass decreased in each group relative to the increase in the amount of body fat. Lipolytic rates, expressed as a function of lean body mass, however, were the same in all three groups. These results suggest that body composition contributes to the regulation of lipolysis during fasting. The decreased rate of lipolysis in subjects who have excess body fat may reflect the decreased need, per unit fat mass, for lipolysis to meet the energy requirements of the lean body mass.     

The impact of body composition on the regulation of lipolysis during short-term fasting

Lipolytic rates were determined in normal-weight young adult (low body fat), normal-weight elderly (moderate body fat), and obese young adult (high body fat) subjects after an overnight (12-15 hr) and short-term (60-87 hr) fasting period. A simultaneous infusion of [1-13C] palmitate acid and [2H5]glycerol was used to measure the inflow of palmitate and glycerol into the bloodstream, and H2 18O dilution was used to measure body composition. The amount of body fat differed between the young adult (11 kg), elderly (23 kg) and obese (49 kg) subjects. Total lean body mass was similar in the normal-weight young adult (60 kg) and obese (63 kg) groups, but was lower in the elderly (46 kg). Lipolytic rates per unit of fat mass decreased in each group relative to the increase in the amount of body fat. Lipolytic rates, expressed as a function of lean body mass, however, were the same in all three groups. These results suggest that body composition contributes to the regulation of lipolysis during fasting. The decreased rate of lipolysis in subjects who have excess body fat may reflect the decreased need, per unit fat mass, for lipolysis to meet the energy requirements of the lean body mass.     

Effect of altering substrate availability on metabolism and performance during intense exercise

The purpose of this study was to determine the effect of altering substrate availability on metabolism and performance during intense cycling. Seven highly trained men ingested a random order of three isoenergetic meals 90 min before cycling at 80% maximal oxygen uptake (VO2max) for 20 min (about 310 W), followed by a 600 kJ time trial lasting about 30 min. Meals consisted of either 1.2 g saturated fat/kg body mass (BM) with 3500 U heparin intravenously (HIFAT) to elevate circulating plasma free fatty acid (FA) concentration, 2.5 g carbohydrate/kg BM (CHO) to elevate plasma glucose and insulin concentrations or 2.5 g carbohydrate +20 mg nicotinic acid/kg BM (NA) to suppress lipolysis and reduce free FA concentration. HIFAT elevated free FA concentration (HIFAT 1.3 (sem 0.2), CHO 0.2 (sem 0.1), NA 0.1 (sem 0.1) mm; P < 0.001) lowered the RER (HIFAT 0.94 (sem 0.01), CHO 0.97 (sem 0.01), NA 0.98 (sem 0.01); P < 0.01) and increased the rate of fat oxidation (HIFAT 24 (sem 3), CHO 12 (sem 2), NA 8 (sem 3) micromol/kg per min; P < 0.01) during the 20 min ride. Marked differences in fat availability and fuel utilisation, however, had little effect on performance in the subsequent time trial (HIFAT 320 (sem 16), CHO 324 (sem 15), NA 315 (sem 13) W). We conclude: (1) increased fat availability during intense cycling increases the rate of fat oxidation; but (2) the reduction in the rate of carbohydrate oxidation in the presence of high circulating plasma free FA is unlikely to enhance intense exercise performance lasting about 1 h; (3) substrate selection during intense (about 80% VO2max) exercise is dominated by carbohydrate oxidation.     

The influence of dairy product consumption on body composition

Recent epidemiologic research suggests that dairy product intake or its components (calcium, vitamin D, and amount or source of protein) are associated with lower body weight or body fat. Clinical intervention trials designed to test this association during weight loss are promising, but still controversial. Few data are available on the effect of calcium or dairy products on prevention of weight gain in long-term trials. The mechanisms proposed to mediate the putative effect of dietary calcium are primarily the formation of fecal fatty acid complexes to reduce fat absorption and the regulation of energy metabolism, including lipolysis from adipocytes and fatty acid oxidation, through the calciotropic hormones, parathyroid hormone, and 1,25-dihydroxyvitamin D. Increased energy expenditure, increased satiety, or a shift from fat to lean mass must accompany these changes in lipid metabolism to achieve changes in fat mass; however, measurable changes in these other parameters either have not been tested or have not been noted uniformly. If dairy products or their components have an effect on altering fat mass, it is likely to be a small change that may have a substantial effect on the incidence of obesity over time.     

Carbohydrates, appetite and feeding behavior in humans

The view of carbohydrates in relation to obesity has changed over the past few decades from being conducive to overconsumption and weight gain to being protective. This article reviews the mechanisms by which carbohydrate is purported to protect against weight gain. Although carbohydrate is metabolized and stored in the body less efficiently than fat, when de novo lipogenesis is invoked on very high carbohydrate diets, the beneficial effect on energy balance is likely to be minimal when typical high fat Western diets are consumed. However, it has been suggested that high carbohydrate foods may influence energy balance by reducing food intake through greater satiety effects, reducing energy density and displacing fat from the diet-the fat-sugar seesaw effect. To date, there seem to be few differences between sugars and starches on satiety and energy intake, but few studies have examined this. Some reduced-fat, and, therefore, higher carbohydrate, foods are highly energy dense. High carbohydrate foods do not necessarily have a low energy density. Evidence from recent studies suggests that adding carbohydrate, and especially sugar, to the diet neither displaces fat from the diet nor protects against elevated energy intake. Although it is easier to overeat on high fat than low fat foods, simply replacing fat with carbohydrate in the diet may not be as protective against overconsumption as the energy density or fat-sugar seesaw arguments suggest.     

Regulation of lipolysis and lipoprotein lipase after weight loss in obese, postmenopausal women

OBJECTIVE: To test the hypothesis that the greater beta-adrenoceptor (beta-AR)-stimulated lipolysis and sensitivity (half-maximal lipolytic response) in abdominal (ABD) adipocytes, greater gluteal (GLT) adipose tissue-lipoprotein lipase (AT-LPL) activity, and dyslipidemia associated with obesity in older women are modifiable by weight loss (WL) and are not due to menopause or aging. RESEARCH METHODS AND PROCEDURES: The metabolic effects of 6 months of hypocaloric diet and low-intensity walking WL program on the regional regulation of in vitro lipolysis and AT-LPL activity in subcutaneous ABD and GLT adipocytes were measured in 34 obese (48.7 +/- 0.7% body fat, mean +/- SE) postmenopausal (59 +/- 1 years) white women. RESULTS: The lipolytic responsiveness to the beta-AR agonist isoproterenol and basal lipolysis in the presence of 1 U/mL adenosine deaminase-uninhibited (lipolysis) were greater (p < 0.01) in ABD than GLT adipocytes before and after WL, but there were no regional differences in postreceptor (dibutyryl 3',5'-cyclic adenosine monophosphate)-stimulated lipolysis. beta-AR sensitivity was greater in ABD than GLT adipocytes before (p < 0.01) but not after WL. Regional AT-LPL did not change after WL, but the change in the activity of ABD (but not GLT) AT-LPL correlated with the baseline adenosine deaminase-uninhibited lipolysis (r = 0.38, p = 0.03). There were no relationships between the declines in plasma triglyceride or increases in high-density lipoprotein cholesterol associated with WL and the changes in regional fat cell metabolism. DISCUSSION: Thus, despite improving lipoprotein lipid profiles in obese, postmenopausal women, WL does not affect the regulation of regional fat metabolism, and a greater tonic inhibition of basal lipolysis by endogenous adenosine may increase the activity of AT-LPL after WL and predispose older women to develop ABD adiposity.     

Low-fat diets, triglycerides and coronary heart disease risk

Nutritionists are currently debating whether low‐fat high‐carbohydrate diets protect against coronary heart disease (CHD). Traditionally, low‐fat diets were prescribed because they reduce plasma and low density lipoprotein (LDL) cholesterol concentrations. However, there is considerable concern because low‐fat diets also increase plasma triglyceride (TG) and reduce high density lipoprotein (HDL) cholesterol concentrations. Recent prospective epidemiological studies have shown that these are independent risk factors for future CHD risk. It has been proposed that the adverse effects of low‐fat, high‐carbohydrate diets on TG and HDL may counteract or negate the beneficial effect of reducing LDL cholesterol concentrations. Although there is also strong epidemiological evidence that reduced total fat intake is not protective against CHD, high‐fat diets predispose to obesity and insulin resistance, both of which adversely affect TG metabolism. This review presents the evidence in relation to the importance of TG as a risk factor for CHD, and explains the pathophysiology that may underlie the aetiological role of TG metabolism in the pathogenesis and progression of CHD. It also addresses the physiological consequences of advocating low‐fat high‐carbohydrate diets, with particular reference to the effects on lipoprotein metabolism and CHD risk.     

妊娠期糖尿病孕妇血脂变化与胎盘脂质转运

正常妊娠时,为了满足胎儿生长发育需要,妊娠期脂代谢将发生巨大变化。这些变化包括早、中孕期脂肪生成增加,晚孕期脂肪分解增加,主要表现为甘油三酯(TG)升高,磷脂和胆固醇也轻度升高。妊娠期糖尿病(GDM)孕妇因胰岛素抵抗(IR),抑制脂肪氧化和分解作用减弱,血脂较正常妊娠更高,并且TG水平与新生儿体重呈正相关。胎盘不能直接转运脂蛋白,TG需水解成脂肪酸才能通过胎盘。胎盘中脂肪酸转运蛋白(FATPs)、胎盘膜脂肪酸结合蛋白(pFABPpm)、脂蛋白脂酶(LPL)和内皮脂肪酶(EL)在脂肪酸转运中起重要作用,GDM孕妇通过增强其表达而影响胎儿生长发育。     

Adipose tissue response to insulin following injury

Derangements of posttraumatic glucose metabolism have long been recognized, with observed changes implicating abnormal action of insulin on target tissues. Insulin is important as well in fat metabolism, and "resistance" to insulin's effects on lipid metabolism after injury has been demonstrated. Although fat-derived fuels are the body's major energy source during starvation and after injury, most studies of posttraumatic insulin "resistance" have focused on carbohydrate metabolism. This study investigated adipose tissue response to insulin in vitro in rats subjected to starvation and/or trauma. Relationships between various parameters, including adipocyte size and weight, plasma glucose, insulin, and glycerol, and basal and insulin-suppressed lipolytic rates, were also studied. Results observed include a decrease in adipocyte size and an increase in basal lipolysis in both starved and traumatized rats, with both decreased sensitivity (T greater than S) and responsiveness (S greater than T) to insulin. These results support the concept that adipocytes of injured animals retain the ability to respond to insulin but lipolytic rates at maximal suppression are still quite high as compared to fed controls. Only minor differences were observed between starved animals and those with starvation and superimposed trauma.     

Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications

Dietary calcium plays a pivotal role in the regulation of energy metabolism; high calcium diets attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Intracellular Ca2+ has a key role in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca2+ resulting in stimulation of lipogenic gene expression and lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. Moreover, we have recently demonstrated that the increased calcitriol released in response to low calcium diets stimulates Ca2+ influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. These findings are further supported by clinical and epidemiological data demonstrating a profound reduction in the odds of being obese associated with increasing dietary calcium intake. Notably, dairy sources of calcium exert a significantly greater anti-obesity effect than supplemental sources in each of these studies, possibly due to the effects of other bioactive compounds, such as the angiotensin converting enzyme inhibitor found in milk, on adipocyte metabolism, indicating an important role for dairy products in the control of obesity.     

Effect of high-fat,high-carbohydrate,and high-protein meals on metabolism and performance during endurance cycling

The effect of pre-exercise meal composition on metabolism and performance in cycling were investigated in a crossover study. Twelve competitive cyclists ingested high-fat, high-carbohydrate, or high-protein meals 90 min before a weekly exercise test. The test consisted of a 1-hour pre-load at 55% peak power, five 10-min incremental loads from 55 to 82% peak power (to measure the peak fat-oxidation rate), and a 50-km time trial that included three 1-km and 4-km sprints. A carbohydrate supplement was ingested throughout the exercise. Relative to the high-protein and high-fat meals, the high-carbohydrate meal halved the peak fat-oxidation rate and reduced the fat oxidation across all workloads by a factor of 0.20 to 0.58 (p =.002-.0001). Reduced fat availability may have accounted for this reduction, as indicated by lower plasma fatty acid, lower glycerol, and higher pre-exercise insulin concentrations relative to the other meals (p =.04-.0001). In contrast, fat oxidation following the high-protein meal was similar to that following the high-fat meal. This similarity was linked to evidence suggesting greater lipolysis and plasma fat availability following high-protein relative to high-carbohydrate meals. Despite these substantial effects on metabolism, meal composition had no clear effect on sprint or 50-km performance.     

Effect of dietary carbohydrate on triglyceride metabolism in humans

When the content of dietary carbohydrate is elevated above the level typically consumed (>55% of energy), blood concentrations of triglycerides rise. This phenomenon, known as carbohydrate-induced hypertriglyceridemia, is paradoxical because the increase in dietary carbohydrate usually comes at the expense of dietary fat. Thus, when the content of the carbohydrate in the diet is increased, fat in the diet is reduced, but the content of fat (triglycerides) in the blood rises. The present article will review studies of carbohydrate-induced hypertriglyceridemia, highlighting data obtained in fasted subjects habituated to high carbohydrate diets, data obtained from subjects in the fed state, and metabolic studies investigating fatty acid and triglyceride synthesis in subjects consuming diets of different carbohydrate content. The available data have been recently expanded by new methodologies, such as the use of stable isotopes, to investigate the metabolism of sugars in humans in vivo. Given the significant increase in body weight observed in the American population over the past decade and the changing availability of carbohydrate in the food supply, future studies of carbohydrate-induced hypertriglyceridemia promise to provide important information of how the macronutrient composition of the diet can influence health.     

Some Musings About Differential Energy Metabolism With Ketogenic Diets

Ketogenic states are of 3 major types: total starvation and those resulting from the consumption of semistarvation, ketogenic diets, and eucaloric ketogenic diets. All are characterized by little or no dietary carbohydrate, resulting in a fat‐based metabolism with sustained ketonemia of varying degrees in each state. The latter 2 diets are clinically useful with important impacts on both aspects of the energy balance equation with increased satiety and less hunger on the intake side and probably increased energy expenditure on the output side; both may have important implications for the successful long‐term management of obesity. Consideration of older research regarding the hormonal response to carbohydrate‐free dieting and recent findings on hepatic glycogen status that occurs with sustained ketonemia support the likelihood that there are profound differences in 24‐hour gluconeogenesis rates between ketogenic diets and balanced diets containing substantial carbohydrate. This metabolic distinction could have a meaningful impact to increase the thermic effect of feeding and daily energy expenditure amounting to 100 kcal/d or more with each of the ketogenic diets.     

The optimal dietary fat to carbohydrate ratio to prevent obesity in the Japanese population: a review of the epidemiological, physiological and molecular evidence

The prevention of obesity, which leads to diabetes and other diseases, is a major concern for public health. There might be an optimal dietary fat to carbohydrate ratio for prevention and treatment of obesity. According to the Japanese Dietary Reference Intakes (RDA) for 2010, the optimal fat intake is 20-30% of energy for ages 1-29 y and 20-25% for ages 30 y and over. Upper boundary values of this recommendation were the median of the percentage of energy from dietary fat in Japanese. In a systematic review to estimate the optimal dietary fat to carbohydrate ratio, it was found that obese subjects with hyperinsulinemia (or insulin resistance) lost more weight on a mild low-carbohydrate (LC) (or low-glycemic load diet; 40% carbohydrate, 30-35% fat) than on a low-fat (LF) diet (55-60% carbohydrate, 20% fat), whereas those without hyperinsulinemia showed the opposite. In non-obese primarily insulin-sensitive subjects, decreasing fat rather than carbohydrate intake is generally more effective to prevent obesity. Physiological and molecular evidence supports this conclusion. Increased carbohydrate intake, especially in high-glycemic food, leads to postprandial hyperglycemia and hyperinsulinemia, which are exaggerated in obese insulin-resistant subjects. Even in an insulin-resistant state, insulin is able to stimulate fatty acid synthesis in liver, activate lipoprotein lipase, and prevent lipolysis in adipose tissues, which all facilitate adipose tissue enlargement. Optimal dietary fat to carbohydrate ratio may differ in populations depending on their prevalence for obesity. Because the prevalence of overweight/obesity in Japanese is low, a LF diet is recommended in the general population.