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Biomedical subjects

L H Storlien

Publications and source records attributed to L H Storlien.

At least 55 records · Page 3Linked to original sources
PubMed1997

Muscle fibre type composition in infant and adult populations and relationships with obesity.

OBJECTIVES: To investigate the fibre type composition of skeletal muscle in infants and young children and to compare the findings to an adult population. To relate the fibre type profile of skeletal muscle in adults to measures of adiposity. DESIGN: Cross-sectional studies of skeletal muscle fibre composition in infants and adults with measures of adiposity in the adults. SUBJECTS: 21 healthy infants and young children (age: 3-21 months) and 40 healthy adult Australian Caucasians (age: 26-62 y; BMI: 18-48 kg/m2). MEASUREMENTS: Skeletal muscle fibre type composition (by myosin ATPase method) and relative body fatness (BMI, waist circumference and waist/hip ratio (WHR)). RESULTS: Infants and young children had significantly lesser proportions of glycolytic Type 2b fibres (6.2 +/- 1.1%; range 0.3-18.9%) compared with adults (20.5 +/- 1.6%; range 4.9-36.0%) (p < 0.0001). The percentage of Type 2b fibres was directly related to BMI (r = 0.44, p = 0.02), waist circumference (r = 0.49, p = 0.009) and WHR (r = 0.44, p = 0.02) in adults. A significant, direct relationship was also found between the proportion of glycolytic Type 2b fibres and age in the adults (r = 0.45, p = 0.01). CONCLUSION: Skeletal muscle fibre type composition is different in infants and adults and there is an age-dependent increase in Type 2b fibres over the lifespan. An increased proportion of glycolytic Type 2b fibres is associated with obesity in adults. Results support a gene-environment interaction on fibre type composition in human skeletal muscle.

Adult↗
PubMed1997

Skeletal muscle triglyceride levels are inversely related to insulin action.

In animal studies, increased amounts of triglyceride associated with skeletal muscle (mTG) correlate with reduced skeletal muscle and whole body insulin action. The aim of this study was to test this relationship in humans. Subjects were 38 nondiabetic male Pima Indians (mean age 28 +/- 1 years). Insulin sensitivity at physiological (M) and supraphysiological (MZ) insulin levels was assessed by the euglycemic clamp. Lipid and carbohydrate oxidation were determined by indirect calorimetry before and during insulin administration. mTG was determined in vastus lateralis muscles obtained by percutaneous biopsy. Percentage of body fat (mean 29 +/- 1%, range 14-44%) was measured by underwater weighing. In simple regressions, negative relationships were found between mTG (mean 5.4 +/- 0.3 micromol/g, range 1.3-1.9 micromol/g) and log10M (r = -0.53, P < or = 0.001), MZ (r = -0.44, P = 0.006), and nonoxidative glucose disposal (r = -0.48 and -0.47 at physiological and supraphysiological insulin levels, respectively, both P = 0.005) but not glucose or lipid oxidation. mTG was not related to any measure of adiposity. In multiple regressions, measures of insulin resistance (log10M, MZ, log10[fasting insulin]) were significantly related to mTG independent of all measures of obesity (percentage of body fat, BMI, waist-to-thigh ratio). In turn, all measures of obesity were related to the insulin resistance measures independent of mTG. The obesity measures and mTG accounted for similar proportions of the variance in insulin resistance in these relationships. The results suggest that in this human population, as in animal models, skeletal muscle insulin sensitivity is strongly influenced by local supplies of triglycerides, as well as by remote depots and circulating lipids. The mechanism(s) underlying the relationship between mTG and insulin action on skeletal muscle glycogen synthesis may be central to an understanding of insulin resistance.

Adult↗
PubMed1996

Skeletal muscle membrane lipids and insulin resistance.

Skeletal muscle plays a major role in insulin-stimulated glucose disposal. This paper reviews the range of evidence in humans and experimental animals demonstrating close associations between insulin action and two major aspects of muscle morphology: fatty acid composition of the major structural lipid (phospholipid) in muscle cell membranes and relative proportions of major muscle fiber types. Work in vitro and in vivo in both rats and humans has shown that incorporation of more unsaturated fatty acids into muscle membrane phospholipid is associated with improved insulin action. As the corollary, a higher proportion of saturated fats is linked to impairment of insulin action (insulin resistance). Studies in vitro suggest a causal relationship. Among polyunsaturated fatty acids (PUFA) there is some, but not conclusive, evidence that omega-3 (n-3) PUFA may play a particular role in improving insulin action; certainly a high n-6/n-3 ratio appears deleterious. In relation to fiber type, the more highly oxidative, insulin-sensitive type 1 and type 2a fibers have a higher percentage of unsaturated fatty acids, particularly n-3, in their membrane phospholipid, compared to the insulin-resistant, glycolytic, type 2b fibers. These variables, however, can be separated and may act in synergy to modulate insulin action. It remains to establish whether lifestyle (e.g., dietary fatty acid profile and physical activity), genetic predisposition, or a combination are the prime determinants of muscle morphology (particularly membrane lipid profile) and hence insulin action.

Animals↗
PubMed1996

Interrelationships between muscle morphology, insulin action, and adiposity.

There is evidence that insulin resistance and obesity are associated with relative increases in the proportion of glycolytic type IIb muscle fibers and decreases in the proportion of oxidative type I fibers. Futhermore, insulin resistance and obesity are associated with the fatty acid (FA) profile of structural membrane lipids. The present study was undertaken to define interrelationships between muscle fiber type and oxidative capacity, muscle membrane FA composition, and insulin action and obesity. Muscle morphology, insulin action, and body fat content were measured in 48 male nondiabetic Pima Indians. Percent body fat (pFAT, determined by hydrodensitometry) correlated negatively with percentage of type I fibers (r = -0.44, P = 0.002) and positively with percentage of type IIb fibers (r = 0.40, P = 0.005). Consistent with this finding, pFAT was also significantly related to oxidative capacity of muscle, as assessed by NADH staining (r = -0.47, P = 0.0007) and citrate synthase (CS) activity (r = -0.43, P = 0.008). Insulin action was correlated with oxidative capacity (CS; r = 0.41, P = 0.01) and weakly correlated with percentage of type IIb fibers (r = -0.29, P = 0.05). In addition, relationships were shown between muscle fiber type and FA composition (e.g., percentage of type I fibers related to n-3 FA; r = 0.37, P = 0.01). Thus leaness and insulin sensitivity are associated with increased oxidative capacity and unsaturation of membranes in skeletal muscle. Present studies support the hypothesis that muscle oxidative capacity and fiber type may play a genetically determined or an environmentally modified role in development of obesity and insulin resistance.

Adipose Tissue↗
PubMed1995

Relationships between muscle membrane lipids, fiber type, and enzyme activities in sedentary and exercised rats.

Insulin resistance in skeletal muscle is associated with 1) relative increases in the proportion of glycolytic and fast-twitch muscle fibers and decreases in the proportion of more oxidative fibers and 2) a higher proportion of the saturated fatty acids in membrane structural lipids. Exercise is known to improve insulin action. The aims of the current studies were 1) to investigate the relationship between muscle fiber type and membrane fatty acid composition and 2) to determine how voluntary exercise might influence both variables. In sedentary Wistar rats in experiment 1, increased amounts of unsaturated fatty acids were found in the more oxidative insulin-sensitive red quadriceps and soleus muscles, whereas reduced levels of polyunsaturated fatty acids were found in primarily glycolytic white quadriceps muscles. In experiment 2, voluntary running-wheel exercise by adult female rats over 45 days resulted in reduced proportions of type IIb fibers (P = 0.01) and increased proportions of type IIa/IIx fibers (P = 0.03) in extensor digitorum longus muscle. The magnitude of these changes was related to the distance run (r = -0.73, P = 0.04; r = 0.79, P = 0.02, respectively). Exercise significantly increased oxidative capacity, as assessed by the proportion of intensely NADH-stained fibers (P = 0.0004) and citrate synthase (P = 0.003) and hexokinase (P = 0.04) activities. Citrate synthase activity was also increased by exercise in soleus muscle, where, as expected, no fiber type changes were detected. No significant differences in the fatty acid profile of soleus and extensor digitorum longus were found between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Skeletal muscle membrane lipid composition is related to adiposity and insulin action.

The cellular basis of insulin resistance is still unknown; however, relationships have been demonstrated between insulin action in muscle and the fatty acid profile of the major membrane structural lipid (phospholipid). The present study aimed to further investigate the hypothesis that insulin action and adiposity are associated with changes in the structural lipid composition of the cell. In 52 adult male Pima Indians, insulin action (euglycemic clamp), percentage body fat (pFAT; underwater weighing), and muscle phospholipid fatty acid composition (percutaneous biopsy of vastus lateralis) were determined. Insulin action (high-dose clamp; MZ) correlated with composite measures of membrane unsaturation (% C20-22 polyunsaturated fatty acids [r= 0.463, P < 0.001], unsaturation index [r= -0.369, P < 0.01]), a number of individual fatty acids and with delta5 desaturase activity (r= 0.451, P < 0.001). pFAT (range 14-53%) correlated with a number of individual fatty acids and delta5 desaturase activity (r= -0.610, P < 0.0001). Indices of elongase activity (r= -0.467, P < 0.001), and delta9 desaturase activity (r= 0.332, P < 0.05) were also related to pFAT but not insulin action. The results demonstrate that delta5 desaturase activity is independently related to both insulin resistance and obesity. While determining the mechanisms underlying this relationship is important for future investigations, strategies aimed at restoring "normal" enzyme activities, and membrane unsaturation, may have therapeutic importance in the "syndromes of insulin resistance."

Adipose Tissue↗
PubMed1995

Amelioration of high-fat feeding-induced insulin resistance in skeletal muscle with the antiglucocorticoid RU486.

Fat feeding produces whole-body insulin resistance and decreased glucose uptake in muscle tissue of rats. To examine the effect of glucocorticoid blockade on the insulin resistance caused by high-fat feeding, four groups of rats were fed diets high in starch (70% of calories) or fat (59% of calories) for 4 weeks with or without the antiglucocorticoid RU486 (69.8 mumol.kg-1.day-1) in the food. Whole-body insulin action was assessed by the euglycemic clamp technique at an upper physiological insulin level with bolus 2-[3H]deoxyglucose to determine individual tissue insulin-stimulated glucose uptake. Whole-body glucose utilization (clamp glucose infusion rate [GIR]) was decreased by high-fat feeding (GIR 68.3 +/- 12.2 vs. 182.6 +/- 12.8 mumol.kg-1.min-1 for the starch-fed group; P < 0.001). Addition of RU486 to the diet significantly improved (GIR 133.9 +/- 12.8 mumol.kg-1.min-1; P < 0.01), but did not fully reverse, the insulin resistance caused by fat feeding. RU486 was without effect in the starch-fed rats. In skeletal muscles, RU486 ameliorated 62 and 68% of the insulin resistance produced by fat feeding in red quadriceps and extensor digitorum longus hindlimb muscles, respectively, but had no effect in heart or white adipose tissue. These results suggest that glucocorticoids play, in a tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by high-fat feeding.

Animals↗
PubMed1994

Insulin action, thermogenesis and obesity.

The case for obesity per se being a major cause of insulin resistance has been made. There is evidence that each of the control points of insulin on glucose metabolism are negatively influenced by lipid oversupply, a characteristic of the obese state. The answer to the corollary, whether insulin resistance (a universal concomitant of obesity) can in turn lead to obesity via a decrease in thermogenesis, is more complex. Overall, the answer would appear to be no. On a population basis, obese individuals would not appear to have lower metabolic rates, whether expressed on a lean tissue or any other basis, than lean individuals. Even in the subpopulation of hypometabolic obese, there are no convincing data that the reduced metabolic rate is linked to particularly severe insulin resistance. Further, improving insulin action by weight loss would not appear to increase thermogenesis as would be predicted if insulin resistance impaired thermogenesis. A case can be made for reductions in a specific aspect of energy expenditure in obesity, that of meal-induced or glucose-induced thermogenesis, and this may be due to insulin resistance. However, meal-induced thermogenesis is a small component of total energy expenditure and total energy expenditure is not different between lean and obese. That leaves the intriguing possibility that a relative failure of prandial thermogenesis has an impact upon energy balance via impairment of satiety (related to reduced metabolic flux) and thus by increasing intake. While a potentially fruitful research avenue, too few data exist on this possibility for it to be anything more than speculative at this stage.

Adult↗
PubMed1994

Dietary fats, membrane phospholipids and obesity.

Modifications in dietary fat profile have been shown to affect body weight gain and adiposity. This may occur through changes in the partitioning between oxidation and storage and/or alterations in membrane structure, which may in turn influence metabolic rate. All the dietary fat classes are substrates for the biosynthetic elongase and desaturase enzymes. Obesity is associated with increased delta 9 desaturase activity, reduced delta 5 desaturase activity and perhaps reduced delta 6 desaturase activity. Dietary lipid profile can affect the activity of each of these enzymes. A number of possible mechanisms linking dietary fat subtypes with development of obesity are discussed, including modification of sodium potassium pump activity and alterations in mitochondrial proton leakage.

Animals↗
PubMed1994

The high-monounsaturated fat diet as a practical alternative for NIDDM.

OBJECTIVE: To examine the dietary preferences of and metabolic effects in patients with non-insulin-dependent diabetes mellitus (NIDDM) of a home-prepared high-monounsaturated fat (HM) diet compared with the recommended high-carbohydrate (CHO) diet. RESEARCH DESIGN AND METHODS: Ten men with mild NIDDM prepared HM and high-CHO diets at home alternately and in random order for 2 weeks each with a minimum 1-week washout. Before and after each diet, 24-h urine glucose, fasting lipids, fructosamine, and 6-h profiles of glucose, insulin, and triglycerides were measured. Dietary preferences were assessed by questionnaire. RESULTS: In the HM diet, patients consumed 40% of energy intake as CHO and 38% as fat (21% monounsaturated) compared with 52 and 24%, respectively, in the high-CHO diet, with equal dietary fiber content. Body weight and total energy intake were similar in both. The HM diet resulted in significantly lower 24-h urinary glucose excretion, fasting triglyceride, and mean profile glucose levels. The fructosamine levels, the fasting total, low-density lipoprotein, and high-density lipoprotein cholesterol, and the prandial triglyceride concentrations did not differ significantly as a result of the diets. The two diets did not differ in ratings for overall acceptance, taste, cost, ease of preparation, variety, or satiety. CONCLUSIONS: Prepared at home, the HM diet was, in the short-term, metabolically better in some aspects than the currently recommended diet for NIDDM. It also provided a palatable alternative.

Adult↗
PubMed1993

The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids.

BACKGROUND: Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS: We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. RESULTS: In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P < 0.001); the average degree of fatty-acid unsaturation (r = -0.61, P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P < 0.01), the average degree of fatty-acid unsaturation (r = 0.62, P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.76, P = 0.007). CONCLUSIONS: Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.

Aged↗