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1.
Int J Obes (Lond) ; 30(7): 1143-8, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16462820

ABSTRACT

OBJECTIVE: To investigate the safety and efficacy for weight loss of simmondsin, a dietary supplement extracted from the seed of the jojoba plant (Simmondsia chinensis). ANIMALS: Sprague-Dawley male rats were fed various levels of simmondsin for 8 weeks (lean rats) or 16 weeks (high fat-induced obese rats). MEASUREMENTS: Food intake, body weight and composition, histopathology, hematology parameters. RESULTS: Simmondsin produced a clear dose-response effect on food intake and body weight. No remarkable histopathologic changes were noted in the liver, kidney and spleen. One lean animal, in the 0.5% group, had approximately a 20% depression in red bone marrow cells. Significant effects on hematology parameters were seen almost exclusively in groups consuming simmondsin at the highest level (0.5%) and these effects appeared to be reversed by removing simmondsin from the diet. CONCLUSION: Simmondsin at both the 0.15% level and the 0.25% level significantly reduced food intake and body weight without apparent negative effects. At dose levels much higher than therapeutic levels, there seemed to be reversible effects on circulating red and white blood cells. Future studies should determine long-term effects of lower doses on blood cell parameters.


Subject(s)
Acetonitriles/therapeutic use , Appetite Depressants/therapeutic use , Cyclohexanes/therapeutic use , Eating/drug effects , Glucosides/therapeutic use , Obesity/drug therapy , Weight Loss/drug effects , Acetonitriles/administration & dosage , Animals , Appetite Depressants/administration & dosage , Body Composition/drug effects , Body Weight/drug effects , Cyclohexanes/administration & dosage , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Glucosides/administration & dosage , Kidney/drug effects , Kidney/pathology , Leukocytes/drug effects , Liver/drug effects , Liver/pathology , Male , Obesity/blood , Obesity/pathology , Obesity/physiopathology , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Thinness/blood , Thinness/physiopathology
2.
Int J Obes (Lond) ; 29(9): 1121-9, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15925959

ABSTRACT

OBJECTIVE: To assess the effect of weight change on the relationship between coffee and tea consumption and diabetes risk. DESIGN: Prospective cohort study, using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow Up Study. Survival analyses were conducted using 301 selfreported cases of diabetes and eight documented diabetes deaths during an 8.4-y follow-up. SUBJECTS: A total of 7006 subjects aged 32-88 y with no reported history of diabetes were included in the study. RESULTS: For all subjects combined, increases in consumption of ground-caffeinated coffee and caffeine at baseline were followed by decreases in diabetes risk during follow-up. There were significant statistical interactions between age and consumption of caffeine (P=0.02) and ground-caffeinated coffee (P=0.03). Age-stratified analysis showed that the decrease in diabetes risk only applied to < or =60-y-old subjects, for whom the decrease in diabetes risk also obtained for ground-decaffeinated coffee and regular tea. The multivariate hazard ratio (HR) and 95% confidence interval for a 2 cups/day increment in the intake of ground-caffeinated coffee, ground-decaffeinated coffee and regular tea was 0.86 (0.75-0.99), 0.58 (0.34-0.99) and 0.77 (0.59-1.00), respectively. The diabetes risk was negatively related to the consumption in a dose-response manner. There were strong statistical interactions between prior weight change and beverage consumption for < or =60-y-old subjects. Further analysis revealed that the decrease in diabetes risk only applied to those who had lost weight, and that there was a positive dose-response relationship between diabetes risk and weight change. For example, the multivariate HR and 95% confidence interval for >0 vs 0 cups/day of ground-decaffeinated coffee was 0.17 (0.04-0.74), 0.52 (0.19-1.42), 0.77 (0.30-1.96) and 0.91 (0.39-2.14) for subgroups with weight change of < or =0, 0-10, 10-20 and >20 lbs, respectively. There was no significant association between diabetes risk and consumption of instant-caffeinated coffee, instant-decaffeinated coffee or herbal tea. Caffeine intake appeared to explain some, but not all, of the diabetes-risk reduction and weight change. CONCLUSION: The negative relationship between diabetes risk and consumption of ground coffee and regular tea, observed for all NHEFS subjects, actually only applied to nonelderly adults who had previously lost weight.


Subject(s)
Caffeine/administration & dosage , Coffee , Diabetes Mellitus, Type 2/etiology , Tea , Weight Loss/physiology , Adult , Age Factors , Aged , Aged, 80 and over , Caffeine/metabolism , Confidence Intervals , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/prevention & control , Dose-Response Relationship, Drug , Drinking , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors
3.
Int J Obes Relat Metab Disord ; 26(5): 593-604, 2002 May.
Article in English | MEDLINE | ID: mdl-12032741

ABSTRACT

OBJECTIVE: To examine long-term safety and efficacy for weight loss of an herbal Ma Huang and Kola nut supplement (90/192 mg/day ephedrine alkaloids/caffeine). DESIGN: Six-month randomized, double-blind placebo controlled trial. SUBJECTS: A total of 167 subjects (body mass index (BMI) 31.8+/-4.1 kg/m(2)) randomized to placebo (n=84) or herbal treatment (n=83) at two outpatient weight control research units. MEASUREMENTS: Primary outcome measurements were changes in blood pressure, heart function and body weight. Secondary variables included body composition and metabolic changes. RESULTS: By last observation carried forward analysis, herbal vs placebo treatment decreased body weight (-5.3+/-5.0 vs. -2.6+/-3.2 kg, P<0.001), body fat (-4.3+/-3.3 vs. -2.7+/-2.8 kg, P=0.020) and LDL-cholesterol (-8+/-20 vs. 0+/-17 mg/dl, P=0.013), and increased HDL-cholesterol (+2.7+/-5.7 vs. -0.3+/-6.7 mg/dl, P=0.004). Herbal treatment produced small changes in blood pressure variables (+3 to -5 mm Hg, P< or =0.05), and increased heart rate (4+/-9 vs. -3+/-9 bpm, P<0.001), but cardiac arrhythmias were not increased (P>0.05). By self-report, dry mouth (P<0.01), heartburn (P<0.05), and insomnia (P<0.01) were increased and diarrhea decreased (P<0.05). Irritability, nausea, chest pain and palpitations did not differ, nor did numbers of subjects who withdrew. CONCLUSIONS: In this 6-month placebo-controlled trial, herbal ephedra/caffeine (90/192 mg/day) promoted body weight and body fat reduction and improved blood lipids without significant adverse events.


Subject(s)
Caffeine/therapeutic use , Ephedra , Ephedrine/therapeutic use , Plant Preparations/therapeutic use , Weight Loss , Blood Glucose/analysis , Blood Pressure/drug effects , Body Composition , Body Weight , Caffeine/administration & dosage , Caffeine/adverse effects , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cola/adverse effects , Dietary Supplements , Electrocardiography, Ambulatory , Ephedra/adverse effects , Ephedra/chemistry , Ephedra sinica/adverse effects , Ephedrine/administration & dosage , Ephedrine/adverse effects , Heart Rate/drug effects , Humans , Patient Compliance , Placebos , Plant Preparations/administration & dosage , Plant Preparations/adverse effects , Prospective Studies , Triglycerides/blood
4.
Int J Obes Relat Metab Disord ; 26(3): 376-83, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11896493

ABSTRACT

OBJECTIVES: To determine whether patterns of sleeping metabolic rate (SMR) are altered in obesity. Specifically to determine the relationship between changes in SMR and body weight, body mass index (BMI, kg/m(2)), and fat-free mass (FFM); and to compare resting metabolic rate (RMR) with SMR during different periods of sleep. SUBJECTS: Eighteen healthy, pre-menopausal, obese (BMI >30, n=9) and non-obese (BMI <30, n=9), female subjects (six Caucasians and 12 African-Americans), with an average age of 36 y (range 22-45). MEASUREMENTS: Total energy expenditure (TEE or 24 h EE), metabolic rate (MR), SMR (minimum, average and maximum) and resting metabolic rate (RMR) or resting energy expenditure (REE) measured by human respiratory chamber, and external mechanical work measured by a force platform within the respiratory chamber. Physical activity index (PAL) was derived as TEE/REE. Body composition was determined by dual-energy X-ray absorptiometry (DXA). RESULTS: SMR decreased continuously during sleep and reached its lowest point just before the subject was awakened in the morning by the research staff. Although averages for RMR and SMR were similar, RMR was lower than SMR at the beginning of the sleeping period and higher than SMR in the morning hours. The rate of decrease in SMR was faster with increasing body weight (-0.829, P<0.0001), BMI (correlation factor -0.896, P<0.0001) and FFM (-0.798, P=0.001). The relationship between the slope of SMR decrease and BMI (y=-5 x 10(-6)x(2)+0.0002x-0.0028) is highly significant, with a P-value of <0.0001 and r(2) value of 0.9622. CONCLUSIONS: The rate of decline in metabolic rate during sleep is directly related to body weight, BMI and FFM. Average SMR tends to be lower than RMR in obese subjects and higher than RMR in non-obese subjects.


Subject(s)
Basal Metabolism , Body Composition , Body Mass Index , Sleep/physiology , Absorptiometry, Photon , Adult , Calorimetry, Indirect , Energy Metabolism , Female , Humans , Kinetics , Obesity/physiopathology , Physical Exertion , Premenopause
5.
Metabolism ; 50(8): 889-93, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11474475

ABSTRACT

Tachyphylaxis to the effects of anorexigenic agents, such as sibutramine (S), may be due, in part, to counterregulatory decreases in energy expenditure (EE) and increases in hunger that result from reduced circulating leptin (L) due to loss of body fat and lowered L production/adipocyte. The present study was conducted to test the hypothesis that L administered at low doses sufficient to restore ambient L to preweight loss concentrations would enhance the intercurrent efficacy of S by reducing the strength of physiologic counterregulation to weight loss. Forty male Sprague-Dawley rats were fed a high-fat (HF) diet (45% energy) to induce obesity. After 8 weeks, the obese rats (600 +/- 58 g) were weight-matched into 4 groups (N = 8/group) and implanted subcutaneously (SC) with 2 mL, 7-day Alzet mini-pumps that provided: vehicle (V, saline), L (0.5 mg/kg/d), S (3 mg/kg/d), or L+S. Food intake (FI) on the HF diet was measured daily. On day 7, 24-hour EE was measured by indirect calorimetry, and the animals then killed for body composition analysis. Compared with vehicle, treatment with S alone, but not L alone, produced significant weight loss (-23 +/- 26 v -6 +/- 16 g, P <.01). L alone, or with S, increased fat oxidation (decreased respiratory quotient [RQ]) compared with V (P <.05). The lack of decline in EE with S may be due to its documented effect to stimulate thermogenesis. Administration of L with S synergistically decreased FI and increased weight loss and fractional fat loss. A reduction in plasma L concentration may contribute to the "plateau phenomenon" observed in studies of weight loss therapies. Replacement doses of L during S administration increased weight loss and fractional fat loss by (1) decreasing food intake and (2) by increasing fat oxidation. Such drug combinations may be useful in the treatment of human obesity.


Subject(s)
Cyclobutanes/pharmacology , Diet , Leptin/pharmacology , Obesity/drug therapy , Animals , Body Composition , Body Weight , Drug Synergism , Energy Intake , Energy Metabolism , Feeding Behavior , Leptin/administration & dosage , Male , Rats , Rats, Sprague-Dawley
6.
Obes Res ; 9(5): 313-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11346673

ABSTRACT

OBJECTIVE: The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure. DISCUSSION: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.


Subject(s)
Carrier Proteins/metabolism , Dietary Fats/pharmacology , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Animals , Calorimetry, Indirect , Dietary Fats/administration & dosage , Energy Metabolism , Fatty Acids, Nonesterified/blood , Ion Channels , Leptin/blood , Male , Mitochondrial Proteins , Permeability , Random Allocation , Rats , Uncoupling Protein 3 , Up-Regulation
7.
Obes Res ; 9(5): 331-6, 2001 May.
Article in English | MEDLINE | ID: mdl-11346676

ABSTRACT

There are many published methods for predicting resting energy expenditure (REE) from measured body composition. Although these published reports extend back almost a century, new related studies appear on a regular basis. It remains unclear what the similarities and differences are among these various methods and what, if any, advantages the newly introduced REE prediction models offer. These issues led us to develop an organizational system for REE prediction methods with the goal of clarifying prevailing ambiguities in the field. Our classification scheme is founded on body composition level (whole-body, tissue-organ, cellular, and molecular) and related components as the REE predictor variables. Each existing REE prediction method by body composition must belong to one body composition level. The suggested classification system, founded on a conceptual basis, highlights similarities and differences among the diverse REE-body composition prediction methods, provides a framework for teaching REE-body composition relationships, and identifies important future research opportunities.


Subject(s)
Basal Metabolism , Body Composition , Models, Biological , Animals , Humans , Models, Theoretical
8.
Am J Physiol Endocrinol Metab ; 280(5): E797-803, 2001 May.
Article in English | MEDLINE | ID: mdl-11287363

ABSTRACT

The effects of fat content in the hypocaloric diet on whole body glucose oxidation and adipocyte glucose transport were investigated in two animal-feeding experiments. Diet-induced obese rats were food restricted to 75% of their previous energy intakes with either a high (45% by calorie) or a low (12% by calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in the 45% compared with the 12% fat group. During the dynamic phase of weight loss (day 10 of food restriction), plasma glucose and insulin concentrations were higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body carbohydrate oxidation rate in response to an oral load of glucose was increased (P < 0.001) by food restriction in both dietary groups; however, carbohydrate oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats during the weight loss period. Adipocyte glucose transport was greater (P < 0.02) in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not in subcutaneous fat. These data suggest that dietary fat content modifies whole body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight loss.


Subject(s)
Carbohydrate Metabolism , Dietary Fats/administration & dosage , Energy Intake , Obesity/metabolism , Obesity/pathology , Weight Loss , Adipocytes/drug effects , Adipocytes/metabolism , Adipose Tissue/pathology , Animals , Blood Glucose/analysis , Diet , Dietary Fats/pharmacology , Glucose/metabolism , Insulin/blood , Insulin/pharmacology , Male , Monosaccharide Transport Proteins/metabolism , Organ Size , Oxidation-Reduction , Rats , Rats, Sprague-Dawley
9.
Int J Obes Relat Metab Disord ; 25(3): 316-24, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11319627

ABSTRACT

OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for weight loss of an herbal supplement containing Ma Huang, Guarana and other ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change. Secondary variables included anthropometric, metabolic and cardiovascular changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32) or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed the study. Active treatment produced significantly (P<0.006) greater loss of weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active treatment also produced greater reductions in hip circumference and serum triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of the 32 placebo-treated control subjects withdrew from the protocol because of potential treatment-related effects. Dry mouth, insomnia and headache were the adverse symptoms reported most frequently by the herbal vs placebo group at the final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana effectively promoted short-term weight and fat loss. Safety with long-term use requires further investigation.


Subject(s)
Caffeine/administration & dosage , Dietary Supplements , Drugs, Chinese Herbal/administration & dosage , Obesity/prevention & control , Theobromine/administration & dosage , Theophylline/administration & dosage , Weight Loss , Adult , Anthropometry , Blood Pressure , Double-Blind Method , Drug Combinations , Female , Heart Rate , Humans , Male , Middle Aged , Triglycerides/blood
10.
Eat Behav ; 2(3): 237-45, 2001.
Article in English | MEDLINE | ID: mdl-15001033

ABSTRACT

Recent studies with rat taste cells treated with polyunsaturated fatty acids suggest that fatty acids may play a role in dietary fat perception. In humans, sensitivity to the textural properties of fat is associated with the genetic ability to taste the bitter compound 6-N-2-propylthiouracil (PROP). However, it has not been shown that PROP tasters are more sensitive in discriminating fatty acids in a high-fat food. Our study with human subjects was designed to test the hypothesis that the ability to orally detect food-grade conjugated linoleic acid added to high-fat vanilla ice cream is associated with the ability to taste PROP. Eighty percent of the PROP tasters in this study, but only 17% of the PROP nontasters correctly discriminated the sample containing the added free fatty acid in a difference test versus unadulterated high-fat vanilla ice cream (Fisher's Exact Test, P=.05). Because most fatty foods contain minute amounts of free fatty acids, further studies with humans examining the contribution of fatty acids to fat perception seem warranted.

11.
Am J Physiol Endocrinol Metab ; 279(3): E539-45, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10950820

ABSTRACT

The relationship between resting energy expenditure (REE) and metabolically active fat-free mass (FFM) is a cornerstone in the study of physiological aspects of body weight regulation and human energy requirements. Important questions, however, remain unanswered regarding the observed linear REE-FFM association in adult humans. This led us to develop a series of REE-body composition models that provide insights into the widely used simple linear REE-FFM prediction model derived experimentally in adult humans. The new models suggest that the REE-FFM relationship in mammals as a whole is curvilinear, that a segment of this function within a FFM range characteristic of adult humans can be fit with a linear equation almost identical to that observed from a composite review of earlier human studies, and that mammals as a whole exhibit a decrease in the proportion of FFM as high metabolic rate organs with greater FFM. The present study thus provides a new approach for examining REE-FFM relationships, advances in a quantitative manner previously observed albeit incompletely formulated REE-body composition associations, and identifies areas in need of additional research.


Subject(s)
Body Composition/physiology , Energy Metabolism/physiology , Rest/physiology , Algorithms , Humans , Models, Biological
12.
Mech Ageing Dev ; 115(1-2): 107-17, 2000 May 18.
Article in English | MEDLINE | ID: mdl-10854633

ABSTRACT

While aging has been found to be a multifactorial process, it seems logical that different aging parameters which reflect the deleterious effects of normal basal metabolism should be directly related. Three such putative aging parameters were therefore measured in adult male Fischer 344 rats on three different long-term diets which have been shown to yield different lifespans. It was found that the daily caloric intake per unit organ weight, a measure of whole-body metabolic rate, was directly proportional to: (1) the level of 8-hydroxydeoxyguanosine in skin dermal cells, used as a measure of the rate of DNA oxidative damage; (2) the proportion of hemoglobin that was glycated, used as a measure of the rate of glycation. This appears to be the first evidence suggesting that whole-body metabolic rate plays a role in determining both the rate of DNA oxidative damage and the rate of glycation involved in aging, because whole-body metabolic rate was the only one of these three variables manipulated in the study. The study also found that there were no significant between-group differences in brain, kidney and liver 8-hydroxydeoxyguanosine, suggesting that DNA oxidative damage in non-mitotic and slow-dividing cells is not a reliable linear biomarker of aging.


Subject(s)
Aging/metabolism , DNA Damage , DNA/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Animals , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Energy Intake , Glycosylation , Hemoglobins/metabolism , Male , Oxidation-Reduction , Rats , Rats, Inbred F344 , Skin/cytology , Skin/metabolism
13.
Metabolism ; 49(4): 503-7, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10778876

ABSTRACT

To investigate the response of plasma leptin and its diurnal variation to graded levels of dietary fat intake, adult (486.8+/-10.8 g), male rats (N = 52) were fed diets containing 12%, 28%, 44%, and 60% fat for 4 weeks. The body weight gain and abdominal fat pad weight were higher (P < .05) in groups fed diets containing 44% and 60% fat compared with the two diets containing less fat. There were no significant differences in terms of body weight or fat pad weight between animals fed the two diets with higher fat content or between animals fed the two lower-fat diets. Twenty-four-hour energy expenditure was not different among the dietary fat groups. After 3 days on the experimental diets, plasma leptin increased (P < .03) in all dietary groups. The increases in leptin in animals fed 12% and 28% fat diets occurred primarily in the morning. In contrast, in groups fed the two diets containing higher fat content, leptin levels increased mainly in the afternoon. As a result, the daily variation in leptin increased (P < .05) in the two groups fed lower-fat diets, but decreased (P < .04) in animals fed the two higher-fat diets. These data demonstrate that short-term high-fat diet feeding abolished the diurnal fluctuation of plasma leptin levels, which may prevent proper leptin function and eventually contribute to the development of obesity.


Subject(s)
Circadian Rhythm/drug effects , Dietary Fats/administration & dosage , Leptin/blood , Animals , Dietary Fats/pharmacology , Energy Intake , Insulin/blood , Male , Osmolar Concentration , Rats , Rats, Sprague-Dawley , Weight Gain/drug effects
14.
Mech Ageing Dev ; 113(1): 37-48, 2000 Jan 24.
Article in English | MEDLINE | ID: mdl-10708248

ABSTRACT

Previous investigators have found the metabolic rate to be the same in calorically-restricted and ad-libitum fed rodents, and hence concluded that the Rate of Living Theory does not help explain the longer lifespan of the calorically-restricted (CR) animal. However, these previous instigators may not have used reliable estimates of metabolic mass in their calculations of metabolic rate. Hence the present study investigated the reliability of ten different estimates of metabolic mass (MM) in 21-month-old male Fischer 344 rats fed three different diets to yield a wide range of body compositions. Two criteria were used to rank each estimate of metabolic mass: strong correlation with daily caloric intake (DCI); and zero Y-intercept on the regression curve of DCI versus the MM. The combined weight of the heart, liver, kidneys and brain (OW) was found to be the best estimate of MM. Statistical analysis of the differences in metabolic rate in the three groups of rats showed that the significance of these differences depended on the estimate of MM used. OW yielded different results than did fat-free mass (FFM), body weight (BW), BW(0.75), and BW(0.67). Therefore, because previous investigators used FFM, BW, BW(0.75), or BW(0.67), rather than a more reliable estimate such as OW, their finding that metabolic rate was not different in the CR and ad-lib groups, and their conclusion that the Rate of Living Theory does not help explain the longer lifespan of the CR animal, are called into question.


Subject(s)
Aging/metabolism , Food Deprivation/physiology , Animals , Body Composition , Diet , Energy Intake , Energy Metabolism , Longevity/physiology , Male , Rats , Rats, Inbred F344
15.
Horm Metab Res ; 31(9): 525-32, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10569255

ABSTRACT

While plasma leptin and adiposity have been found to be strongly related, the specific nature of this relationship has yet to be clarified. Hence, plasma leptin and three indicators of adiposity were measured in adult male Fischer 344 rats on three different long-term diets: continuous ad libitum feeding; ad libitum feeding until early adulthood, then continuous 60% caloric restriction; and ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, then ad libitum feeding for 5 months. Body fat was found to be a good linear correlate of plasma leptin, with a zero Y-intercept, and a constant plasma leptin-body fat ratio. The number of adipocytes per rat and % body fat were strong quadratic correlates of plasma leptin. This study is the first to find a zero Y-intercept and constant plasma leptin-body fat ratio, probably because it is the first to simultaneously measure both plasma leptin and body fat accurately, and to account for confounders such as gender, genetic background, age, physical activity, and possibly obesity. The study also explored the effect of switching calorically-restricted rats to ad libitum feeding. This led to a rapid rise, and then synchronized up-down cycles in average daily food intake and body weight, with a steady upward trend toward a new stable body-weight set point. It is hypothesized that this pattern resulted from two simultaneous feedback mechanisms, possibly involving leptin. In conclusion, this study suggests that, under controlled conditions, the plasma leptin-body fat ratio is a constant for a particular mammalian strain, independent of dietary history.


Subject(s)
Adipose Tissue/metabolism , Leptin/blood , Analysis of Variance , Animals , Energy Intake , Feedback , Linear Models , Male , Obesity/metabolism , Rats , Rats, Inbred F344
16.
Metabolism ; 48(10): 1272-7, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10535390

ABSTRACT

Previous studies of the relationship between plasma leptin and energy usage have yielded contradictory findings. The present study was therefore conducted to clearly distinguish and measure the energy usage rate and the energy usage rate adjusted for a surrogate of metabolically active tissue mass. We investigated the simultaneous relationships between these two measures of energy usage, leptin, and body fat in 21-month-old adult male Fischer 344 rats on three different long-term dietary regimens: (1) continuous ad libitum feeding (Ad-lib); (2) ad libitum feeding until early adulthood, and then continuous 60% caloric restriction (CR); and (3) ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, and then ad libitum feeding for 5 months (CR/Ad-lib). Two versions of the daily usage rate were measured: daily dietary caloric intake (DCI), and daily energy expenditure (EE) based on indirect calorimetry. Two versions of the metabolically active tissue mass were also measured: fat-free mass (FFM), and the sum of the weight of the heart, brain, liver, and kidneys. Energy usage rates were adjusted for these measures of metabolically active tissue mass to yield measures of the energy metabolic rate. Correlation, regression, and path analyses showed that both the energy usage rate and adjusted energy usage rate played important independent roles in determining body fat and plasma leptin, but only after multivariate techniques were used to account for the simultaneous interactions between variables. Increases in the energy usage rate were associated with increases in body fat and the adjusted energy usage rate. Increases in the adjusted energy usage rate were associated with decreases in body fat and plasma leptin. These findings suggest that differences in subjects adjusted energy usage rate could explain some of the apparently contradictory findings concerning the relationship between energy usage and plasma leptin in previously published studies. In conclusion, this appears to be the first study to clearly separate and quantify the effects of the energy usage rate and adjusted energy usage rate on body fat and plasma leptin. The findings suggest that under conditions of long-term stable body weight, both of these measures of energy usage play independent simultaneous roles in determining body fat and plasma leptin.


Subject(s)
Adipose Tissue/anatomy & histology , Energy Metabolism/physiology , Leptin/blood , Animals , Calorimetry, Indirect , Energy Intake , Food Deprivation , Male , Organ Size , Rats , Rats, Inbred F344
17.
Neuron ; 23(3): 537-48, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10433265

ABSTRACT

To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.


Subject(s)
Energy Metabolism/physiology , Gene Deletion , Neurons/metabolism , Proteins/genetics , Proteins/metabolism , Aggression/physiology , Animals , Arcuate Nucleus of Hypothalamus/chemistry , Arcuate Nucleus of Hypothalamus/cytology , Arcuate Nucleus of Hypothalamus/metabolism , Body Weight/physiology , Catecholamines/metabolism , Circadian Rhythm/physiology , Fasting/physiology , Female , Fertility , Gene Expression/physiology , Gonadotropins/metabolism , Homeostasis/physiology , In Situ Hybridization , Leptin , Male , Mammary Glands, Animal/chemistry , Mammary Glands, Animal/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Growth Factors , Neurons/chemistry , Neuropeptides , Ovary/chemistry , Ovary/metabolism , Oxygen Consumption/physiology , Phenotype , Pituitary Gland/chemistry , Pituitary Gland/metabolism , Protein Precursors/genetics , Protein Precursors/metabolism , RNA, Messenger/analysis , Thyrotropin/genetics
18.
Am J Physiol ; 274(5): E860-6, 1998 05.
Article in English | MEDLINE | ID: mdl-9612244

ABSTRACT

Although the study of human body composition is advancing rapidly, confusion still prevails regarding the molecular-level lipid component. Most molecular-level body composition models are presently based on the overall hypothesis that nontriglyceride lipids constitute an insignificant proportion of total body lipid. A single lipid or "fat" component consisting of triglycerides is thus assumed in most molecular-level body composition models. To test this hypothesis, the present study, carried out in adult rats, was designed to examine two questions: 1) What is the proportion of total lipids as triglycerides? and 2) Is this proportion constant or does it change with negative energy balance and weight loss produced by calorie restriction and increased exercise? Results indicated that with negative energy balance and weight loss there were progressive losses of total body triglyceride and lipid. The proportion of total lipids as triglyceride was 0.83 +/- 0.08 (SD) in control animals, with reductions at 2 and 9 wk of energy restriction [0.82 +/- 0.04 (P = NS vs. control) and 0.70 +/- 0.15 (P = 0.05)] and at 9 wk for energy restriction plus exercise [0.67 +/- 0.09 (P = 0.003)]. Nontriglyceride lipids comprised 2.8% of carcass weight at baseline and decreased to 2.2% by 9 wk of energy restriction and exercise (P = NS). Substantial differences were observed between body composition ratios expressed as percentages of the lipid-free body mass (LFM) and triglyceride-free body mass (TGFM); (e.g., total body water/LFM and TGFM in controls = 72.7 +/- 0.7 and 70.4 +/- 2.2, respectively; P = 0.02). These observations strongly support the existence and importance of nontriglyceride lipids as a body composition component that responds independently from storage triglycerides, with negative energy balance produced by food restriction and exercise.


Subject(s)
Body Composition/physiology , Energy Metabolism/physiology , Lipid Metabolism , Models, Biological , Triglycerides/metabolism , Animals , Body Water/metabolism , Body Weight/physiology , Female , Kinetics , Rats , Rats, Sprague-Dawley
20.
Appl Radiat Isot ; 49(5-6): 731-2, 1998.
Article in English | MEDLINE | ID: mdl-9569593

ABSTRACT

The precision and accuracy of a prompt-gamma neutron activation facility developed to assess total body protein in rats is estimated. The coefficient of variation of nitrogen measurement, as estimated by repeated measurements on 15 rats, was 5.5% for an equivalent dose of 60 mSv (Q = 20). Good agreement was observed in comparing the results of in vivo neutron activation analysis and chemical carcass analysis performed by the Kjeldahl method. The application of the technique in comparing the effect of a low-fat and a high-fat diet on body protein in rats is demonstrated.


Subject(s)
Body Composition , Phantoms, Imaging , Proteins/analysis , Analysis of Variance , Animals , Diet, Fat-Restricted , Dietary Fats , Gamma Rays , Monte Carlo Method , Neutron Activation Analysis/methods , Nitrogen/analysis , Rats , Reproducibility of Results
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