PubMed Health⌕ Search

Biomedical subjects

Barbara A Gower

Publications and source records attributed to Barbara A Gower.

At least 19 recordsLinked to original sources

IGF-I polymorphism is associated with lean mass, exercise economy, and exercise performance among premenopausal women.

BACKGROUND: We undertook this study to investigate the association of a genetic polymorphism of the insulin-like growth factor, IGF-I(189), on body composition, exercise performance and exercise economy, after controlling for the independent effect of race as assessed by African genetic admixture (AFADM). METHODS: A total of 114 premenopausal sedentary women were genotyped for IGF-I189, obtaining measures of fat mass, lean body mass, VO2 during cycling and stairclimbing, time on treadmill and leg strength. A quantitative value for AFADM was derived from genotypic information of approximately 40 ancestry informative markers and used as covariate in statistical models. RESULTS: After adjusting for AFADM, IGF-I189 was negatively associated with lean body mass (p = 0.029) and lean leg mass (p = 0.050). Leg strength was not associated with the presence/absence of IGF-I189 (p = 0.380), but carriers of the allele demonstrated a longer time on the treadmill (p = 0.015) after adjusting for AFADM. There was also a negative relationship between oxygen uptake during cycling and presence of the IGF-I189 independent of AFADM (p = 0.010). CONCLUSIONS: Independent of AFADM, individuals with IGF-I189 are more likely to have low leg lean mass and to perform better in activities requiring exercise economy and endurance performance.

Adult↗

Difference in dietary intake between women with polycystic ovary syndrome and healthy controls.

OBJECTIVE: To test the hypothesis that the dietary intake and dietary composition of women with polycystic ovary syndrome (PCOS) is associated with indices of glycemic status. We hypothesized that women with PCOS would consume a diet higher in total energy, fat, and specific foods with a high glycemic index than would healthy, control-group women and that dietary composition would be associated with indices of insulin resistance and secretion among women with PCOS. DESIGN: Cohort study. SETTING: Research center on a university campus. PATIENT(S): Thirty women with PCOS and 27 healthy, age-, race-, and body mass index (BMI)-matched control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Nutrient intake data were collected from a food questionnaire and a 4-day food record. Fasting sera were analyzed for concentrations of insulin and glucose; estimates of insulin resistance were calculated. RESULT(S): Consumption of total energy, macronutrients, micronutrients, and high glycemic index foods was similar between the groups. However, the PCOS group consumed significantly more white bread (7.9 +/- 4.4 vs. 5.5 +/- 2.9 servings over 4 days) and tended to consume more fried potatoes than did the control group (1.0 +/- 1.5 vs. 0.4 +/- 0.7 servings over 4 days). The PCOS group had a significantly greater fasting insulin concentration (22.5 +/- 14.9 vs. 15.1 +/- 8.3 muIU/mL) and a significantly lower glucose-to-insulin ratio (4.7 +/- 2.1 vs. 7.6 +/- 5.2) than the control group. Within the PCOS group, HOMA-IR and HOMA-%beta-cell function were significantly associated with BMI. The HOMA-IR, HOMA-%beta-cell, fasting insulin, and glucose-to-insulin ratio were not positively associated with measures of diet composition. CONCLUSION(S): Compared with matched control women, women with PCOS exhibited a dietary pattern that was marked by consumption of a greater amount of specific foods with a high glycemic index; however, diet composition was not associated with the greater fasting insulin concentration or with lower glucose-to-insulin ratio that was observed in the PCOS group.

Adult↗

Validity of new child-specific thoracic gas volume prediction equations for air-displacement plethysmography.

BACKGROUND: To determine the validity of the recently developed child-specific thoracic gas volume (TGV) prediction equations for use in air-displacement plethysmography (ADP) in diverse pediatric populations. METHODS: Three distinct populations were studied: European American and African American children living in Birmingham, Alabama and European children living in Lisbon, Portugal. Each child completed a standard ADP testing protocol, including a measured TGV according to the manufactures software criteria. Measured TGV was compared to the predicted TGV from current adult-based ADP proprietary equations and to the recently developed child-specific TGV equations of Fields et al. Similarly, percent body fat, derived using the TGV prediction equations, was compared to percent body fat derived using measured TGV. RESULTS: Predicted TGV from adult-based equations was significantly different from measured TGV in girls from each of the three ethnic groups (P < 0.05), however child-specific TGV estimates did not significantly differ from measured TGV in any of the ethnic or gender groups. Percent body fat estimates using adult-derived and child-specific TGV estimates did not differ significantly from percent body fat measures using measured TGV in any of the groups. CONCLUSION: The child-specific TGV equations developed by Fields et al. provided a modest improvement over the adult-based TGV equations in an ethnically diverse group of children.

Black or African American↗

Relationship between insulin sensitivity and in vivo mitochondrial function in skeletal muscle.

Recent data have shown that individuals with low insulin sensitivity (S(I)) also have reduced whole body maximal oxygen uptake. The objectives of this study were to determine 1) whether muscle mitochondrial function was independently related to S(I) after being adjusted for known determinants of S(I) and 2) whether lower S(I) among African-American (AA) vs. Caucasian-American (CA) women was due to lower muscle mitochondrial function among AA women. Subjects were 37 CA and 22 AA premenopausal women (age: 33.6 +/- 6.3 yr). Mitochondrial function [time constant of ADP (ADP(tc))] was assessed during a 90-s unilateral isometric contraction using (31)P magnetic resonance spectroscopy, S(I) with an intravenous glucose tolerance test, body composition by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) with computed tomography. ANOVA was used to compare AA and CA groups, and multiple linear regression modeling was used to identify independent predictors of S(I). Between-race comparisons indicated that muscle oxidative capacity was lower among AAs vs. CAs (ADP(tc): 25.6 +/- 9.8 vs. 21.4 +/- 9.9 s). Multiple linear regression models for the dependent variable S(I) contained 1) VAT and race and 2) VAT, race, and ADP(tc). Significant independent effects for all predictor variables were observed in both the first (r(2) = 0.345) and second (r(2) = 0.410) models. The partial correlation for race was lower in the second model (-0.404 vs. -0.300), suggesting that muscle mitochondrial function contributed to the racial difference in S(I). Lower muscle mitochondrial function among AAs may in part explain lower S(I) among them.

Absorptiometry, Photon↗

Role of diet in the treatment of polycystic ovary syndrome.

OBJECTIVE: To determine whether eucaloric diets either enriched with monounsaturated fatty acids (MUFA; 17% energy) or low in carbohydrates (Low CHO; 43% energy) would increase insulin sensitivity (Si) and decrease circulating insulin concentrations, relative to a standard diet (STD; 56% CHO, 31% fat, 16% protein), among women with polycystic ovary syndrome (PCOS). DESIGN: Crossover. SETTING: Academic research environment. PATIENT(S): Healthy women with PCOS not on hormonal or insulin-sensitizing therapy. INTERVENTION(S): Subjects consumed three, 16-day, eucaloric diets, each separated by a 3-week washout period. A frequently sampled, intravenous, glucose tolerance test was administered at baseline and following each diet. MAIN OUTCOME MEASURE(S): Fasting glucose, insulin, the acute insulin response to glucose (AIRg), Si, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, A4, total cholesterol, high-density lipoprotein cholesterol (HDL-C), tryglycerides (TG), and free fatty acids (FFA). RESULT(S): Fasting insulin was lower following the Low CHO diet relative to the STD diet; AIRg was lower following the Low CHO diet relative to the MUFA diet. Fasting glucose, Si, and the circulating concentrations of reproductive hormones were not significantly affected by the intervention. CONCLUSION(S): A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS, which, over time, may improve reproductive/endocrine outcomes.

Adult↗

Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty.

OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin secretion, and beta-cell function during puberty in white and black youth. STUDY DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance test and minimal modeling were used to measure SI, the acute insulin response to glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46) and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years). Growth curve models (including 272 observations) with SI, AIRg, and DI regressed on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting for covariates, growth curve models revealed that SI decreased and subsequently recovered by the end of puberty in whites and blacks (both p < .05), AIRg decreased linearly across Tanner stages in both races (both p < .001), and DI decreased across puberty in blacks (p = .001) but not in whites (p = .2). CONCLUSIONS: White and black youth exhibited transient insulin resistance and diminished AIRg during puberty. The progressive decline in DI among blacks versus whites may reflect a unique effect of puberty on beta-cell compensation in blacks. Future studies are needed to identify whether this difference contributes to the increased risk of type II diabetes in young blacks.

Black or African American↗

Changes in intra-abdominal fat in early postmenopausal women: effects of hormone use.

OBJECTIVE: Intra-abdominal fat (IAF) accumulates with age, is greater among postmenopausal vs. premenopausal women, and is linked to risk for both type 2 diabetes and cardiovascular disease. Whether hormone replacement therapy (HRT) prevents or attenuates changes in IAF and related risk factors is not clear. The objectives of this observational study were to 1) determine whether HRT attenuated the expected age-related increase in IAF and 2) identify the independent effects of HRT and fat distribution on changes in disease risk factors. RESEARCH METHODS AND PROCEDURES: Subjects were early postmenopausal white women 45 to 55 years of age. Women either used HRT at the time of enrollment (n = 33) or did not (n = 17). Subjects were evaluated at baseline and 2 years for body composition (DXA), body fat distribution (computed tomography), insulin sensitivity (Si; minimal model), and serum lipids. RESULTS: IAF increased significantly over 2 years, and this increase was not attenuated by HRT. HRT users had less IAF throughout the study. HRT users showed an increase in Si, whereas non-users showed a decrease. Superficial subcutaneous adipose tissue was significantly and independently related to total cholesterol, whereas IAF was related to high-density lipoprotein cholesterol, triglycerides, and Si. DISCUSSION: HRT users had less IAF at baseline and throughout the study. Whether HRT altered the relationship between total body fat and IAF or whether differences between groups existed before the study should be addressed through a randomized, interventional study design. HRT had a significant effect on Si; IAF and superficial subcutaneous adipose tissue were significant determinants of disease risk factors.

Age Factors↗

Increased resting energy expenditure after 40 minutes of aerobic but not resistance exercise.

OBJECTIVE: Resting energy expenditure (REE) is increased 24 hours after high-intensity aerobic exercise lasting 60 minutes, whereas results have been inconsistent after resistance training and aerobic exercise of shorter duration. The objective of the study was to compare the effects of 40 minutes of high-intensity aerobic vs. resistance exercise on REE 19 to 67 hours after exercise. RESEARCH METHODS AND PROCEDURES: REE was compared 19, 43, and 67 hours after 40 minutes of aerobic training (AT; 80% maximum heart rate) or resistance training (RT; 10 repetitions at 80% maximum strength, two sets and eight exercises). Twenty-three black and 22 white women were randomly assigned to AT, RT, or no training (controls). Exercisers trained 25 weeks. REE was measured after a 12-hour fast. RESULTS: There was a significant time x group interaction for REE when adjusted for fat-free mass and fat mass, with post hoc tests revealing that the 50-kcal difference between 19 and 43 hours (1310 +/- 196 to 1260 +/- 161 kcal) and the 34-kcal difference between 19 and 67 hours (1310 +/- 196 to 1276 +/- 168 kcal) were significant for AT. No other differences were found, including RT (19 hours, 1256 +/- 160; 43 hours, 1251 +/- 160; 67 hours, 1268 +/- 188 kcal). Urine norepinephrine increased with training only in AT. After adjusting for fat-free mass, REE Delta between 19 and both 43 and 67 hours was significantly related to urine norepinephrine (r = 0.76, p < 0.01 and 0.68, p < 0.03, respectively). DISCUSSION: Consistent with findings on longer duration AT, these results show that 40 minutes of AT elevates REE for 19 hours in trained black and white women. This elevation did not occur with 40 minutes of RT. Results suggest that differences are, in part, due to increased sympathetic tone.

Adipose Tissue↗

Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women.

Recently, the transcription factor 7-like 2 (TCF7L2) gene on chromosome 10q25.2 has been linked with type 2 diabetes among Caucasians, with disease associations noted for single nucleotide polymorphisms (SNPs) rs12255372 and rs7903146. To investigate mechanisms by which TCF7L2 could contribute to type 2 diabetes, we examined the effects of these SNPs on clinical and metabolic traits affecting glucose homeostasis in 256 nondiabetic female subjects (138 European Americans and 118 African Americans) aged 7-57 years. Outcomes included BMI, percent body fat, insulin sensitivity (S(i)), acute insulin response to glucose (AIR(g)), and the disposition index (DI). Homozygosity for the minor allele (TT) of SNP rs12255372 occurred in 9% of individuals and was associated with a 31% reduction in DI values in a recessive model. The at-risk allele TT was also associated with lower AIR(g) adjusted for S(i) in both ethnic groups, whereas rs12255372 genotype was not associated with measures of adiposity or with S(i). The T allele of rs12255372 was also associated with increased prevalence of impaired fasting glucose. Genotypes at rs7903146 were not associated with any metabolic trait. Lower S(i) and higher AIR(g) observed in the African-American compared with the European-American subgroup could not be explained by the TCF7L2 genotype. Our data suggest that the TCF7L2 gene is an important factor regulating insulin secretion, which could explain its association with type 2 diabetes.

Adult↗

Early ethnic difference in insulin-like growth factor-1 is associated with African genetic admixture.

IGF-1 is a growth-promoting hormone. Numerous studies have reported higher systemic concentrations of IGF-1 among African Americans (AA) compared with European Americans (EA) before puberty. We conducted this cross-sectional analysis to determine whether African ancestral genetic background, dietary factors, energy expenditure, adiposity, and socioeconomic status contribute to this difference. Children were prepubertal, AA and EA males and females. Genetic admixture was assessed from approximately 20 ancestry informative genetic markers. Body composition was determined by dual-energy x-ray absorptiometry; intake of energy, carbohydrate, protein, and fat by 24-h dietary recall; activity-related energy expenditure by doubly labeled water and indirect calorimetry; and socioeconomic status (SES) according to the Hollingshead scale. IGF-1 and IGF binding protein-3 (IGFBP-3) were measured using immunoradiometric assays. AA children had significantly greater IGF-1 compared with EA children (p < 0.01). In addition, AA children had lower SES and greater protein intake relative to EAs (p < 0.05 for both). Multiple linear regression analysis revealed that the only significant independent predictors of IGF-1 were IGFBP-3 and African admixture (p < 0.01 for both). Thus, our data suggest that the greater IGF-1 of AA relative to EA children could have a genetic basis.

Adiposity↗

Synergistic heterozygosity in mice with inherited enzyme deficiencies of mitochondrial fatty acid beta-oxidation.

We have used mice with inborn errors of mitochondrial fatty acid beta-oxidation to test the concept of synergistic heterozygosity. We postulated that clinical disease can result from heterozygous mutations in more than one gene in single or related metabolic pathways. Mice with combinations of mutations in mitochondrial fatty acid beta-oxidation genes were cold challenged to test their ability to maintain normal body temperature, a sensitive indicator of overall beta-oxidation function. This included mice of the following genotypes: triple heterozygosity for mutations in very-long-chain acyl CoA dehydrogenase, long-chain acyl CoA dehydrogenase, and short-chain acyl CoA dehydrogenase genes (VLCAD+/-//LCAD+/-//SCAD+/-); double heterozygosity for mutations in VLCAD and LCAD genes (VLCAD+/-//LCAD+/-); double heterozygosity for mutations in LCAD and SCAD genes (LCAD+/-//SCAD+/-); single heterozygous mice (VLCAD+/-, LCAD+/-, SCAD+/-) and wild-type. We found that approximately 33% of mice with any of the combined mutant genotypes tested became hypothermic during a cold challenge. All wild-type and single heterozygous mice maintained normal body temperature throughout a cold challenge. Despite development of hypothermia in some double heterozygous mice, blood glucose concentrations remained normal. Biochemical screening by acylcarnitine and fatty acid analyses demonstrated results that varied by genotype. Thus, physiologic reduction of the beta-oxidation pathway, characterized as cold intolerance, occurred in mice with double or triple heterozygosity; however, the derangement was milder than in mice homozygous for any of these mutations. These results substantiate the concept of synergistic heterozygosity and illustrate the potential complexity involved in diagnosis and characterization of inborn errors of fatty acid metabolism in humans.

Acclimatization↗

Dietary fat intake and insulin resistance in black and white children.

OBJECTIVE: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. RESEARCH METHODS AND PROCEDURES: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24-hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above-AMDR/within-AMDR guidelines), and differences were analyzed by 2 x 2 analysis of covariance, adjusting for covariates. RESULTS: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above-AMDR compared with within-AMDR blacks) and was not seen in whites. DISCUSSION: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.

Adolescent↗

Apolipoprotein A-II polymorphism and visceral adiposity in African-American and white women.

To determine the association between the -265 T to C substitution in the apolipoprotein A-II (APOA-II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African-American and white women, we genotyped 237 women (115 African-American and 122 white) for this polymorphism. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. In addition to VAT, we examined the association between the polymorphism and other phenotypes (total body fat, total abdominal adipose tissue, and subcutaneous abdominal adipose tissue). The mutant C allele in the APOA-II gene was less frequent in African-American compared with white women, 23% vs. 36%, respectively (p < 0.01). VAT was significantly higher in carriers of the C allele compared with noncarriers after adjustment for total body fat (p < 0.05). When separate analyses by ethnic group were conducted, the association between the polymorphism and VAT was observed in white (p < 0.05) but not African-American (p = 0.57) women. There was no association between the polymorphism and the other phenotypes. These results indicate a significant association between the T265C APOA-II polymorphism and levels of VAT in premenopausal women. This association is present in white but not African-American women.

Absorptiometry, Photon↗

Adiponectin is lower among African Americans and is independently related to insulin sensitivity in children and adolescents.

Adiponectin is inversely related to adiposity and positively correlated with insulin sensitivity (S(i)). Sparse data exist on the contributions of ethnicity and body fat distribution to variance in serum adiponectin. Hypotheses tested were that adiponectin would be lower in African Americans compared with Caucasians; that adiponectin would be inversely related to central, not peripheral, fat; that adiponectin would be positively associated with S(i); and that baseline adiponectin would predict change in S(i) over 2 years in 150 African-American and Caucasian youth. Multiple linear regression modeling showed that adiponectin was lower in African-American versus Caucasian children (adjusted means 10.8 +/- 0.5 vs. 12.3 +/- 0.5 microg/ml, respectively; P < 0.05); inversely related to trunk fat (P < 0.05); and positively related to limb fat (P < 0.01). Addition of the acute insulin response to glucose to the model eliminated the significance of ethnicity. S(i), which was positively related to adiponectin (P < 0.05), was lower in African Americans (P < 0.001) and girls (P < 0.05). Baseline adiponectin did not predict change in S(i) over 2 years. In conclusion, adiponectin was positively correlated with S(i), inversely related to central fat, and positively related to peripheral fat. In addition, higher acute insulin response to glucose explained lower adiponectin among African-American children.

Adipose Tissue↗

Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism and abdominal adipose tissue in African-American and Caucasian women.

Genetic variants in the intestinal fatty acid-binding protein-2 (FABP2) gene have been associated with body composition phenotypes. We examined the association between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n = 103) and Caucasian (n = 120) women. Subjects were genotyped for the marker. In addition, body composition was assessed by dual energy x-ray absorptiometry, and VAT was determined from a single computed tomography scan. The frequency of the Thr mutant allele did not differ significantly by ethnic group. After adjusting for total body fat, total abdominal adipose tissue (TAT) and SAAT were significantly lower in carriers of either one or two copies of the mutant Thr allele (P < 0.01). There was no association between total fat mass or VAT and the FABP2 polymorphism. Separate analyses by ethnic group showed that the association between the polymorphism and TAT and SAAT was observed in Caucasian (P < 0.01), but not in African-American (not significant), women. We conclude that women carriers of the FABP2 Thr allele have lower TAT and SAAT than noncarriers of the mutation. This association is present in Caucasian, but not in African-American, women.

Abdomen↗

Weight loss and race modulate nitric oxide metabolism in overweight women.

Weight reduction is associated with a decrease in the risk of developing cardiovascular disease. We hypothesized that, given the central role of reactive oxygen and nitrogen species in vascular biology, changes in nitric oxide (NO) metabolism contribute to benefits of weight loss. In a controlled weight loss trial involving overweight (body mass index (BMI) = 27-30 kg/m(2)), otherwise healthy premenopausal Caucasian and African-American women, serum levels of nitrite and nitrate, as an index of NO production, and protein 3-nitrotyrosine and myeloperoxidase (MPO), as markers of inflammation, were determined. Testing was performed before and after reduction to normal body weight (BMI < 25) under standardized conditions, with controlled diet, and following 1 month of weight maintenance. After weight loss there was an increase in nitrite and nitrate, and levels were higher among African-American women relative to Caucasian counterparts. Whereas weight loss was associated with a decrease in 3-nitrotyrosine in Caucasian women, no change was observed among African-Americans. Furthermore, MPO levels increased in response to weight loss for African-Americans, but did not change in Caucasian women. These data indicate that vascular production of reactive nitrogen species can be modulated by race and weight loss and highlight important racial differences in these responses and are discussed in the context of risk for developing vascular disease.

Adult↗

Weight change affects serum leptin and corticosterone in the collared lemming.

The aim of this study was to determine whether photoperiod-induced changes in body and fat mass are accompanied by changes in leptin and corticosterone concentrations in collared lemmings. At weaning, eighty male lemmings were maintained in either long photoperiod (LD, n = 40 ) or short photoperiod (SD, n = 40 ). Ten weeks post-weaning lemmings were weighed and assigned to a secondary photoperiod that consisted of either remaining in the same photoperiod or being transferred to the alternate photoperiod (LD-LD, LD-SD, SD-SD, and SD-LD; n = 20 per group). Ten days post-switch, half the animals from each group were sacrificed. The remaining animals were sacrificed on day 21 post-switch. Blood was collected for determination of serum leptin and corticosterone, and carcasses were analyzed for body composition. LD-SD lemmings gained the most weight, whilst SD-LD lemmings lost weight. SD-LD lemmings had significantly lower leptin levels relative to fat mass than SD-SD lemmings. Corticosterone levels were higher in the SD-LD than SD-SD lemmings on both days 10 and 21. Levels were not significantly different between LD-LD and LD-SD lemmings; however by day 21 the levels were slightly lower in the LD-SD lemmings. Discussion. Lemmings showed seasonally appropriate body weight changes in response to the changing photoperiod. Weight loss was associated with higher corticosterone, and lower leptin levels adjusted for fat mass. Neither relative leptin levels, nor corticosterone levels changed significantly with weight gain. Our results indicate that corticosterone and leptin are associated more with seasonal weight loss than weight gain in lemmings.

Animals↗

Influence of dietary fatty acid chain-length on metabolic tolerance in mouse models of inherited defects in mitochondrial fatty acid beta-oxidation.

Fasting-induced metabolic disease of all inherited deficiencies of the acyl-CoA dehydrogenases is characterized by hypoglycemia, hypoketonemia, and organic aciduria. Mice with these enzyme deficiencies are cold intolerant. To evaluate the potential role that dietary fatty acid chain-length has on a patient's ability to compensate during a metabolic challenge, we fed long-chain acyl CoA dehydrogenase (LCAD) deficient and short-chain acyl CoA dehydrogenase (SCAD) deficient mice a diet rich in medium-chain triglycerides (MCT) or long-chain triglycerides (LCT). To elucidate the importance of maintaining adequate serum glucose concentrations on compensation mechanisms during metabolic challenge, we treated LCAD-/- mice with a solution of 12.5% glucose or saline prior to fasting and a cold-challenge. We found that feeding SCAD deficient mice the LCT diet from weaning increased survival from 40 to 94% during metabolic challenge of cold tolerance. In contrast, there was no benefit to feeding the MCT diet at weaning to LCAD-/- mice; however, there was significant benefit when LCAD-/- mice were fed the MCT diet from the beginning of gestation. Survival during cold-challenge increased from 50 to 93%. In the LCAD-/- mice treated with glucose, despite maintaining serum glucose concentrations at normal or higher concentrations, the LCAD-/- mice were still unable to compensate during metabolic challenge. These results indicate the important influences dietary fatty acids may have by providing enhanced metabolic tolerance in patients with inborn errors of fatty acid oxidation. Furthermore, these studies demonstrate that there may be crucial variables involved in the treatment of these patients, including the patient's specific enzyme deficiency, the quantity and chain-length of dietary fat, which may provide positive effects, as well as the time in development when it was administered.

Acyl-CoA Dehydrogenase, Long-Chain↗