Biomedical subjects

L H Storlien

Publications and source records attributed to L H Storlien.

At least 37 records · Page 2Linked to original sources

PubMed2000

Beneficial effects of increasing monounsaturated fat intake in adolescents with type 1 diabetes.

This study aimed to increase the monounsaturated fat content in the diet of outpatient adolescents with type 1 diabetes and to examine the metabolic effects after 12 weeks. Twenty-three adolescents were randomly allocated to either a high monounsaturated fat diet or a control diet. Their mean age was 16.9 (S.D. 2.1) years and median HbA(1c) was 9.1% [IQR 7.9-10.4%]. Dietary targets were not reached judged by their 4-day food diaries. However, the whole study group had a significant increase in monounsaturated fat as indexed by red cell phospholipid fatty acids (RCFAs), with an increase of n-9 RCFAs from 14.9% [IQR: 14.5-21.7%] to 21.7% [IQR: 18.8-25.6%] (P=0.002). Changes in n-9 RCFAs were inversely related to changes in HbA(1c) (R(2)=0.26, P=0.02), such that a 10% increase in n-9 RCFAs corresponded to a 0.64% improvement (decrease) in HbA(1c). Changes in n-9 RCFAs were also inversely related to changes in plasma total cholesterol (R(2)=0.38, P=0.002) and plasma LDL cholesterol (R(2)=0. 21, P=0.03). These changes were not associated with changes in insulin dose, body weight or physical activity. Overall, the results demonstrate that a modest increase in the monounsaturated fat content of an adolescent diet has the potential to improve glycaemic control and lipid profile.

Adolescent↗

PubMed2000

Diet composition and insulin action in animal models.

Critical insights into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by strictly controlled dietary interventions not possible in human studies. Overall, the literature has moved from a focus on macronutrient proportions to understanding the unique effects of individual subtypes of fats, carbohydrates and proteins. Substantial evidence has now accumulated for a major role of dietary fat subtypes in insulin action. Intake of saturated fats is strongly linked to development of obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is not. This is consistent with observations that saturated fats are poorly oxidized for energy and thus readily stored, are poorly mobilized by lipolytic stimuli, impair membrane function, and increase the expression of genes associated with adipocyte profileration (making their own home). PUFAs have contrasting effects in each instance. It is therefore not surprising that increased PUFA intake in animal models is associated with improved insulin action and reduced adiposity. Less information is available for carbohydrate subtypes. Early work clearly demonstrated that diets high in simple sugars (in particular fructose) led to insulin resistance. However, again attention has rightly shifted to the very interesting issue of subtypes of complex carbohydrates. While no differences in insulin action have yet been shown, differences in substrate flux suggest there could be long-term beneficial effects on the fat balance of diets enhanced in slowly digested/resistant starches. A new area of major interest is in protein subtypes. Recent results have shown that rats fed high-fat diets where the protein component was from casein or soy were insulin-resistant, but when the protein source was from cod they were not. These are exciting times in our growing understanding of dietary factors and insulin action. While it has been clear for some time that 'oils ain't oils', the same is now proving true for carbohydrates and proteins.

Animals↗

PubMed2000

Does obesity influence foot structure in prepubescent children?

OBJECTIVE: This study examines the relationship between obesity and foot structure in prepubescent children. DESIGN: Field-based, experimental data on BMI (body mass index) and foot structure were collected for 431 consenting children from 18 randomly selected primary schools. SUBJECTS: Of the 431 participants, 62 obese (BMI>95th percentile) and 62 non-obese (10th percentile 90th percentile) children (age = 8.5+/-0.5 y) were selected. MEASUREMENTS: Height and weight were measured to calculate BMI. Static weight-bearing footprints for the right and left foot of each subject were then taken using a pedograph to calculate the Footprint Angle and the Chippaux-Smirak Index as representative measures of the surface area of the foot in contact with the ground. RESULTS: A significant difference was found between the Footprint Angle of the obese and non-obese subjects for both the left (t = 3.663; P<0.001) and right (t = 3.742; P<0.001) feet whereby obese subjects displayed a reduced angle. Chippaux-Smirak Index scores were also significantly different for both the left (t = -6.362; P<0.001) and right (t=-5.675; P<0.001) feet between the two subject groups where a greater score for the obese subjects was evident. A decreased footprint angle and an increased Chippaux-Smirak Index are characteristic of structural foot changes that have been associated with compromised foot function. CONCLUSIONS: Excess body mass appears to have a significant effect on the foot structure of prepubescent children whereby young obese children display structural foot characteristics which may develop into problematic symptoms if excessive weight gain continues. Further investigation into possible consequences, particularly any effects on foot function, is warranted.

Body Mass Index↗

PubMed2000

Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice.

OBJECTIVE: To investigate the development of high fat diet-induced obesity and leptin resistance. DESIGN: Two experiments were carried out in this study. Firstly, we fed the mice with a high- or low-fat diet for up to 19 weeks to examine a progressive development of high fat diet-induced obesity. Secondly, we examined peripheral and central exogenous leptin sensitivity in mice fed high- or low-fat diets for 1, 8 or 19 weeks. SUBJECTS: A total of 168 C57BL/6J mice (3 weeks old) were used in this study. MEASUREMENTS: In the first experiment, we measured the body weight, energy intake, adipose tissue mass, tibia bone length, and plasma leptin in mice fed either a high- or low-fat diet for 1, 8, 15 and 19 weeks. In the second experiment, body weight change and cumulative energy intake were measured at 6 h intervals for 72 h after leptin injection in mice fed a high- or low-fat diet for 1, 8 or 19 weeks. RESULTS: The results from the first experiment suggested that the development of high fat diet-induced obesity in mice could be divided into early, middle and late stages. Compared with the mice fed a low-fat diet, the mice fed a high-fat diet showed a gradually increased body weight (+5.2%), fat storage (epididymal plus perirenal; +6.7%) and plasma leptin (+18%) at 1 week; +11.4%, +68.1%, and +223%, respectively, at 8 weeks; and +30.5%, +141%, and +458%, respectively, at 19 weeks. Energy intake of high fat diet-fed mice was equal to that of low fat diet-fed controls for the first 3 weeks; it fell below control levels over the next 5 week period, but began to increase gradually after 8 weeks of high-fat diet feeding and then increased dramatically from 15 weeks to be 14% higher than that of controls after 19 weeks. The results from our second experiment showed that: (1) after 1 week of feeding, the mice fed a high-fat diet were sensitive to a 2 microg/g (body weight) intraperitoneal (i. p.) injection of leptin, with no differences in body weight change or cumulative energy intake post-injection; (2) after 8 weeks of feeding, the mice fed a high-fat diet were insensitive to 2 microg/g (body weight) i.p. leptin, but were sensitive to a 0.1 microg intracerebroventricular (i.c.v.) injection of leptin; (3) after 19 weeks of feeding, the mice fed a high-fat diet were insensitive to 0. 1 microg i.c.v. leptin, but were sensitive to a high dose of 2 microg i.c.v. leptin. CONCLUSIONS: The present study demonstrated that the development of high fat diet-induced obesity (19 weeks) in C57 B1/6J mice could be divided into three stages: (1) an early stage in response to high-fat diet that mice were sensitive to exogenous leptin; (2) a reduced food intake stage when mice had an increase in leptin production and still retained central leptin sensitivity; and (3) an increased food intake stage, accompanied by a reduction of central leptin sensitivity.

Animals↗

PubMed2000

Effects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjects.

Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal. NA did not significantly alter 24-h mean systolic or diastolic blood pressure. Fasting glucose, insulin and non-esterified free fatty acid (NEFA) levels remained unchanged, energy expenditure and substrate oxidation were not altered by NA. These results suggest a short term reduction in insulin sensitivity with NA is not accompanied by a change in blood pressure. This may relate to the short duration of treatment, to a dissociation between insulin resistance and hypertension or to other homeostatic mechanisms which prevent blood pressure rising in subjects not predisposed to hypertension.

Adult↗

PubMed2000

Dietary variables and glucose tolerance in pregnancy.

OBJECTIVE: To investigate relationships between dietary macronutrient intakes and glucose tolerance in pregnancy RESEARCH DESIGN AND METHODS: Nulliparous pregnant Chinese women diagnosed with gestational diabetes mellitus (GDM) (n = 56) were compared to age-, gestational age-, height-, and parity-matched groups with normal glucose tolerance (n = 77) and glucose intolerance (IGT) (n = 38) based on the results of an oral glucose tolerance test (National Diabetes Data Group criteria), performed between 24 and 28 weeks of pregnancy. A 24-h recall dietary assessment was also obtained at the time of screening. RESULTS: Subjects with IGT and GDM were significantly heavier (66.1 +/- 1.4 and 68.6 +/- 1.2 kg, respectively, mean +/- SEM) (P < 0.0001) than the normal group (61.2 +/- 1.8 kg) and had a higher BMI. Overall energy intake was similar between groups, as were the intakes of each macronutrient (%kcal). However, there was a highly significant reduction in polyunsaturated fat intake in the IGT and GDM groups whether expressed as %kcal, % of total fat, or fat kcal. This effect was independent of body weight or BMI whether assessed by ordinal logistic regression or by analysis of a weight- and BMI-matched subgroup of the subjects (P = 0.002 for %kcal; n = 47 normal, 26 IGT, and 43 GDM subjects). In logistic regression analysis of the complete data set, increased body weight (P < 0.0001) and decreased polyunsaturated fat intake (P = 0.0014) were both independent predictors of glucose intolerance (IGT and GDM), as were increased body weight and a low dietary polyunsaturated to saturated fat ratio. CONCLUSIONS: Increased polyunsaturated fat intake is associated with a reduced incidence of glucose intolerance during pregnancy. This finding may have major implications for dietary management of women with or at risk of developing GDM.

Adult↗

PubMed2000

Role of dietary factors: macronutrients.

Insulin resistance is an important early marker of the metabolic syndrome disease cluster. Our understanding of the role of dietary macronutrients in the etiology of insulin resistance is currently limited by a paucity of credible intervention studies in humans. In contemplating such studies there are many issues that need consideration from actual study design (e.g., duration of intervention, study population, cross-over or not, nutrient formulation) to practical issues such as palatability and compliance (i.e., that terribly important issue of achievability because realistically individuals must be "free range" in order to complete studies of sufficient duration). Initiatives to support well-designed multicenter studies on diet and insulin resistance would have a major impact on our ability to treat, but more importantly to prevent, the metabolic syndrome diseases.

Animals↗

PubMed1999

Influence of dietary fats on c-Fos-like immunoreactivity in mouse hypothalamus.

The hypothalamus is a brain region of major importance in regulation of energy balance via autonomic nervous control of both intake and expenditure. There is substantial evidence that diets high in saturated fats lead to obesity while diets equally high in polyunsaturated fats (PUFAs) do not. Using c-Fos as a marker, this study aimed to investigate hypothalamic neuronal response in mice fed high fat diets (58% of calories as fat) emphasising saturated, n-3 or n-6 polyunsaturated fatty acids, or a low fat (10% of calories) diet over periods of 1 and 7 weeks. In addition, a 4-week "reversal" intervention with n-3 polyunsaturated or low fat diet was undertaken in saturated fat-fed mice. Food intake and body weight were measured over the feeding periods. At 1, 7 and 11 weeks mice were killed, epididymal fat pad were weighed and brains were removed for quantitation of hypothalamic c-Fos-like immunoreactive (FLI) neurons. Weight gain, and epididymal fat pad weight, were highest on the saturated fat diet and lowest on the n-3 diet despite similar food intakes (epididymal fat weight at week 7: saturated fat, 622+/-48 mg; n-6 fat 423+/-69; low fat 387+/-10, n-3 fat 225+/-26). Compared to a low fat diet, FLI neurons in the dorsal part of lateral hypothalamic (dLH) area was dramatically increased by saturated fat feeding (+367% at 1 week) while ventromedial hypothalamic (VMH) activity was decreased. In contrast with n-6 and n-3 feeding dLH FLI neuronal activity was unchanged but actually increased in the VMH. Paraventricular nucleus (PVN) FLI neurons increased in the high saturated group only at 7 and 11 weeks, after substantial fat accumulation. Substitution of saturated fat diet with the n-3 diet partially reversed (48%) the increase in FLI neurons in PVN of saturated fat-fed mice, while it significantly increase FLI neurons in arcuate nucleus (+400%). In summary, this study demonstrates that dietary saturated fat modulates hypothalamic neuronal activity in a pattern (high lateral, reduced ventromedial activity) consistent with its obesogenic effects. In contrast, diets equally high in PUFA (particularly of the n-3 class) neither increase adiposity nor derange the lateral/medial neuronal activity balance.

Animals↗

PubMed1999

Interrelationships between muscle fibre type, substrate oxidation and body fat.

OBJECTIVE: To investigate interrelationships between muscle fibre type, respiratory exchange ratio (RER) during exercise at a fixed workload and adiposity. DESIGN: Cross-sectional study. SUBJECTS: 21 untrained, healthy male subjects. MEASUREMENTS: Body fat composition by dual-energy X-ray absorptiometry (DEXA). Exercise test at 55% of VO2max, muscle fibre type composition, muscle NADH and citrate synthase enzyme activity levels; serum insulin, glucose and cortisol concentrations. RESULTS: Percent body fat was inversely correlated to the proportion of type I muscle fibres (r=-0.55, P<0.02). In addition percent trunk fat was negatively correlated with percent type I fibres (r=-0.58, P<0.01) while this relationship was not present for percent leg fat. There was no relation between RER at rest or during exercise and muscle fibre type composition or percent body fat. CONCLUSION: Body fat and percent type I muscle fibres were correlated, supporting skeletal muscle fibre type as a potential etiological factor in obesity. No correlation was observed between percent body fat and substrate oxidation at rest or during moderate exercise, indicating that muscle fuel substrate mix does not appear to provide a mechanism for this relation under either condition.

Adult↗

PubMed1999

Regular exercise modulates muscle membrane phospholipid profile in rats.

We investigated the effect of regular exercise and changes in dietary fatty acid profile on skeletal muscle phospholipid fatty acid profile in rats. Rats were randomly divided into three groups and for 4 wk fed either a carbohydrate-rich diet (CHO, 10 percent of total energy (E%) fat, 20 E% protein, 70 E% CHO) or one of two fat-rich diets (65 E% fat, 20 E% protein, 15 E% CHO) containing predominantly either saturated or monounsaturated fatty acids. Each dietary group was randomly assigned to a trained (6 d/wk, progressive to 60 min, 28 m/min at a 10 degrees incline) or a sedentary group. The effect of training was apparent in the three hindlimb muscles analyzed: red quadriceps, white quadriceps and soleus. The unsaturation index was significantly lower in the trained than in the sedentary groups (206 +/- 2 vs. 215 +/- 2, P < 0. 01), which largely reflected a lower content of arachidonic acid [20:4(n-6): 14.5 +/- 0.5 vs. 16.6 +/- 0.4% of total fatty acids, P < 0.01] and docosahexaenoic acid [22:6(n-3): 11.1 +/- 0.2 vs. 11.7 +/- 0.3% of total fatty acids, P < 0.03] and a concomitant higher content of linoleic acid [18:2(n-6): 20.0 +/- 0.4 vs. 17.8 +/- 0.4% of total fatty acids, P < 0.01]. Training affected skeletal muscle membrane structural composition, and this occurred independently of dietary fatty acid changes. This change likely reflects an increased utilization of highly unsaturated fatty acids for energy, an effect which may have deleterious effects on insulin action.

Animals↗

PubMed1999

Relationships between maternal risk of insulin resistance and the child's muscle membrane fatty acid composition.

In adult humans, insulin resistance is associated with relatively low proportions of polyunsaturated fatty acids (PUFAs) in muscle membrane structural lipid. The aim of the present study was to determine the relationship between young children's muscle membrane fatty acid (FA) composition and indices of insulin resistance in their mothers. Muscle biopsy specimens obtained at the time of elective surgery from 83 children (54 boys), aged 0.78 +/- 0.05 year (mean +/- SE), were analyzed for phospholipid FA composition. Fasting blood samples were collected from the mothers of the children, and maternal BMIs were calculated. Stepwise multiple regression analysis showed that after accounting for the effect of breast-feeding, log maternal insulin levels were inversely associated with the child's muscle membrane docosahexaenoic acid (22:6 n-3; R2 = 0.29, P = 0.0006) and the sum of the n-3 PUFAs (R2 = 0.23, P = 0.0016) but positively associated with the sum of the n-6 PUFAs (R2 = 0.05, P = 0.03) and the n-6/n-3 PUFA ratio (R2 = 0.20, P = 0.007). Independent of breast-feeding, log maternal triglyceride levels were inversely associated with the child's muscle membrane unsaturation index (a measure of unsaturation) (R2 = 0.08, P = 0.005). Maternal BMI; total, LDL, and HDL cholesterol; and the child's age, sex, and birth weight were not significant predictors of the child's muscle membrane FA composition. Thus, maternal fasting insulin and triglyceride levels are significant predictors of the FA composition of the child's muscle membrane. The less unsaturated muscle membranes in children whose mothers have higher fasting insulin and triglyceride levels may reflect a genetic reluctance to incorporate PUFAs into membranes, thus predisposing them to insulin resistance syndromes.

Adult↗

PubMed1998

Insulin sensitivity, muscle fibre types, and membrane lipids.

One of the key abnormalities of non-insulin-dependent diabetes mellitus (NIDDM) and related diseases of the "Metabolic Syndrome" is impaired insulin action (insulin resistance). Since skeletal muscle plays a major role in insulin-stimulated glucose uptake and whole-body energy expenditure, it is a central player in carbohydrate and lipid metabolism, and hence in the balance between health and disease. This manuscript seeks to describe the evidence both for involvement in insulin resistance of three major muscle variables: membrane lipid composition, storage triacylglycerol and fibre type mixture; and for the interrelationships between these variables. Taken with results provided in other chapters in this volume, the literature described gives insights into the role that certain dietary fats and physical inactivity may play in the development of insulin resistance and hence the disease cluster of the Metabolic Syndrome.

Animals↗

PubMed1998

The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children.

Long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid ([DHA] 22:6 n-3), are important components of cell membranes. Low levels of DHA and other LCPUFAs in skeletal muscle membrane phospholipid are associated with insulin resistance and obesity in adults. These findings may be influenced by both dietary and genetic factors. This study aimed to investigate the interrelationships between the type of infant feeding, skeletal muscle phospholipid fatty acid (FA) composition, and glucoregulation in young children. Skeletal muscle biopsies and fasting blood samples were obtained from 56 normally nourished young children (35 males and 21 females) aged less than 2 years (mean +/- SE, 0.76 +/- 0.06) undergoing elective surgery. The dietary history was taken, and muscle phospholipid FA composition was analyzed. Subgroups of totally breast-fed and age-matched formula-fed infants were compared. Breast-fed infants (n = 13; age, 0.54 +/- 0.06 years) had a significantly higher percentage of DHA (3.63% +/- 0.22% v 1.84% +/- 0.11%, P < .0001) and total percentage of LCPUFAs (30.24 +/- 0.87% v 25.17% +/- 0.86, P < .0001) in muscle phospholipids compared with the formula-fed group (n = 12; age, 0.59 +/- 0.08 years). The totally breast-fed group had lower plasma glucose levels than the formula-fed group (4.7 +/- 0.2 v 5.4 +/- 0.2 mmol/L, P < .02). Consistent with these findings, further analysis of a group of 39 children who had either never or not recently been breast-fed showed significant inverse correlations between fasting plasma glucose and the percentage of both DHA (r = -.47, P < .003) and total LCPUFAs (r = -.38, P < .05). The results of this study show that (1) breast-feeding increases LCPUFA levels in skeletal muscle membrane and (2) early development of relatively higher levels of LCPUFAs in the phospholipid of skeletal muscle, influenced both by type of feeding and by genetic predisposition, is associated with lower fasting plasma glucose. Early changes in skeletal muscle membrane phospholipid FA saturation may play a role in the subsequent development of diseases associated with insulin resistance.

Biopsy↗

PubMed1998

The actions of a novel lipoprotein lipase activator, NO-1886, in hypertriglyceridemic fructose-fed rats.

High circulating fasting and prandial triglyceride levels are associated with both insulin resistance and the development of cardiovascular disease. The aim of this investigation was to study the effects of NO-1886, a novel lipoprotein lipase (LPL) activator, on triglyceride levels, fat oxidation, and glucose tolerance in fructose-fed rats, a hypertriglyceridemic model of insulin resistance. Adult male Wistar rats were fed for 4 weeks with a high-starch diet or a high-fructose diet without and with NO-1886 (50 mg x kg[-1] x d[-1] orally). Fructose feeding increased plasma triglyceride levels, an effect that was ameliorated by NO-1886 treatment (week 1/week 4: starch-fed, 2.4 +/- 0.1/2.8 +/- 0.2 mmol/L; fructose-fed, 3.6 +/- 0.5/5.5 +/- 0.5; fructose + NO-1886, 2.7 +/- 0.2/3.6 +/- 0.3). The mean 24-hour respiratory quotient (RQ) was significantly lower in the fructose + NO-1886 group compared with fructose-fed rats, indicating increased oxidation of fat. Fructose feeding elevated liver triglyceride levels by 74% (P < .01), an effect not altered by NO-1886. Red and white quadriceps hindlimb muscle triglyceride levels were not different between groups. Glucose tolerance (intravenous test in long-term cannulated rats) was mildly deteriorated and fasting insulin and glucose levels were elevated in fructose-fed rats, effects which were ameliorated by NO-1886. In conclusion, in the fructose-fed rat model of hypertriglyceridemia and insulin resistance, addition of a LPL activator reduced circulating triglyceride levels without causing increased muscle triglyceride accumulation or deterioration in glucose tolerance. LPL activators may prove to be a fruitful avenue to explore in the search for new therapeutic agents in the treatment of dyslipidemias and insulin resistance.

Animals↗

PubMed1998

Polyunsaturated fatty acids, membrane function and metabolic diseases such as diabetes and obesity.

Lipids play an extraordinary range of roles in normal and deranged metabolism. In diabetes and obesity, lipids have often been seen just as impacting on the energy balance equation. New data are extending our understanding of how lipid subclasses influence carbohydrate and lipid metabolism at multiple control points: from the modulation of membrane proteins to the regulation of gene transcription.

Animals↗

PubMed1998

Endurance in high-fat-fed rats: effects of carbohydrate content and fatty acid profile.

The purpose of this experiment was to study endurance performance and substrate storage and utilization in fat- or carbohydrate-fed rats. Ninety-nine rats were randomly divided into three groups and over 4 wk were fed either a carbohydrate-rich [CHO; 10% total energy content in the diet (E%) fat, 20 E% protein, 70 E% carbohydrate] diet or one of two fat-rich diets (65 E% fat, 20 E% protein, 15 E% carbohydrate) containing either saturated (Sat) or monounsaturated fatty acids (Mono). Each dietary group was randomly assigned to a trained (6 days/wk, progressive to 60 min, 28 m/min at a 10% incline) or a sedentary group. Rats were killed either before or after a treadmill endurance run to exhaustion. Training increased endurance (206%), but diet composition did not affect endurance in either trained or sedentary rats. beta-Hydroxyacyl-CoA dehydrogenase activity was increased in fat-fed but not carbohydrate-fed rats (P < 0.05). Respiratory exchange ratio during the initial phase of exercise was lower after the Mono compared with the Sat diet (P < 0. 05) and higher after the CHO than the Sat diet (P < 0.05). Thus adaptation to a high-fat diet containing a moderate amount of carbohydrates did not induce enhanced endurance in either trained or untrained rats; however, substrate utilization was modulated by both amount and type of dietary fat during the initial stage of exercise in trained and sedentary rats.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1997

Does dietary fat influence insulin action?

What is clear from the research thus far is that dietary fat intake does influence insulin action. However, whether the effect is good, bad, or indifferent is strongly related to the fatty acid profile of that dietary fat. The evidence has taken many forms, including in vitro evidence of differences in insulin binding and glucose transport in cells grown with different types of fat in the incubation medium, in vivo results in animals fed different fats, relationships demonstrated between the membrane structural lipid fatty acid profile and insulin resistance in humans, and finally epidemiological evidence linking particularly high saturated fat intake with hyperinsulinemia and increased risk of diabetes. This contrasts with the lack of relationship, or even possible protective effect, of polyunsaturated fats. In particular, habitual increased n-3 polyunsaturated dietary fat intake (as fish fats) would appear to be protective against the development of glucose intolerance. It is reassuring that the patterns of dietary fatty acids that appear beneficial for insulin action and energy balance are also the patterns that would seem appropriate in the fight against thrombosis and cardiovascular disease. Mechanisms, though, still need to be defined. However, there are strong indicators that defining the ways in which changes in the fatty acid profile of membrane structural lipids are achieved, and in turn influence relevant transport events, plus understanding the processes that control accumulation and availability of storage lipid in muscle may be fruitful avenues for future research. One of the problems of moving the knowledge gained from research at the cellular level through to the individual and on to populations is the need for more accommodating research designs. In vitro studies may provide in-depth insights into intricate mechanisms, but they do not give the "big picture" for practical recommendations. On the other hand, correlational studies tend to be fairly blunt instruments, requiring large numbers that are very often not feasible if a greater depth of understanding of the biological processes is to be incorporated. There may be benefit in turning to the clinical case study as a framework for a more comprehensive analysis of the links between dietary fats and insulin action. The real challenge is to keep the depth of analysis rigorous enough to be able to explain and accommodate individual variation (i.e., the diversity of both environmental and genetic backgrounds) while at the same time satisfying the cultural need to provide appropriate overall dietary guidelines. Finally, David Kritchevsky brought to our attention a delightful quote from Mark Twain: "There is something fascinating about science. One gets such a wholesale return of conjecture for such a trifling investment of fact." In the field of dietary fats and the Metabolic Syndrome, this quotation is, unfortunately, apt. Much more research is necessary to define how dietary fats really work to affect insulin action. Well designed, long-term studies in "free range" humans must be undertaken if dietary guidelines for the Metabolic Syndrome are to be based on anything more than a "trifling" amount of "fact."

Animals↗

PubMed1997

Fatty acids, triglycerides and syndromes of insulin resistance.

Muscle plays a major role in insulin-stimulated glucose disposal. There is now a range of evidence in humans and experimental animals demonstrating strong relationships between the fatty acid composition of structural membrane lipids and insulin action. The in vivo work is correlative but the in vitro studies suggest a causal relationship exists. Good insulin action is associated with an increased proportion of n-3 fatty acids, low saturates, a low n-6/n-3 ratio and possibly increased monounsaturates. What is reassuring is that there is a pleasing symmetry with the fatty acid pattern that might lead to decreased thrombosis. There is little argument about saturated fats with a reduction having a range of beneficial effects. However, the n-3 fatty acids might also be a key to amelioration of both insulin resistance and thrombosis. The sites of action of n-3s are multiple: decreased triglyceride and VLDL production; inhibition of thromboxane A2 production, increased thromboxane A3 and decreased platelet aggregation; reduction of triglyceride and VLDL concentration; improved blood rheology and membrane transport; action on the endothelium and proliferation of the intimal cells, and improvement of vascular tone. The data here are now strong and reasonably consistent. Similarly, after initial controversy, the evidence for n-3s playing a beneficial role in insulin action is now accumulating. The n-6 PUFAs are a bit of a worry: while arachidonic acid levels in muscle phospholipid has linked positively to insulin action in our studies, linoleic is negative. Linoleic acid, in high amounts, is known to inhibit the delta6 fatty acid desaturase enzyme and with the competition between n-6 and n-3 fatty acids for the enzymes of desaturation and elongation it does focus on a high n-6/n-3 ratio as a critical factor in both insulin resistance and atherosclerosis.

Animals↗