Biomedical subjects

I D Caterson

Publications and source records attributed to I D Caterson.

At least 37 records · Page 2Linked to original sources

PubMed1996

Changes in glucose and lipid metabolism following weight loss produced by a very low calorie diet in obese subjects.

OBJECTIVE: To study the effects of a very low calorie diet (VLCD) on glucose and lipid metabolism in obese subjects, in particular, the effects on insulin sensitivity and the activities of the key enzymes of glucose disposal, glycogen synthase (GS) and the pyruvate dehydrogenase complex (PDHC). DESIGN: Clinical dietary intervention study (1.67 MJ (400 kcal)/day) until weight loss of > 10%. SUBJECTS: 11 (seven male, four female) non-diabetic, obese subjects (age: 27-62 y; BMI: 40.5 +/- 1.4 kg/m2). MEASUREMENTS: Whole body glucose disposal (by euglycemic hyperinsulinemic clamp), respiratory quotient (RQ), resting energy expenditure (REE), glucose and lipid oxidation (by indirect calorimetry), insulin-stimulated PDHC and GS activity (in muscle biopsies) both before and immediately after VLCD (i.e. while still in a hypocaloric state), serum hormone and metabolite levels throughout the dietary period. RESULTS: Weight loss was accompanied by reduced insulin and elevated NEFA levels, improved insulin sensitivity due to increased nonoxidative glycolysis with no increase in PDHC or GS activities. The rate of weight loss was inversely related to the initial RQ. PDHCa was strongly age-related. CONCLUSION: A low RQ may be used as a predictor of the efficacy of VLCD treatment and that while VLCD improves nonoxidative glycolytic flux, changes in oxidative glucose disposal and muscle glucose storage are prevented by high NEFA availability during this catabolic phase of dietary intervention.

Adult↗

PubMed1996

A shared care approach in obesity management: the general practitioner and a hospital based service.

OBJECTIVE: To describe the process of establishing a Shared Care obesity management programme between general practitioners and a hospital based specialist obesity service and to compare outcomes of the Shared Care programme (SC) to an established hospital based programme (MOS). DESIGN: A comparative study of two obesity management programmes. Patients were matched on gender, age and BMI (kg/m2). SUBJECTS: 29 female and eight male (age: 47.0 +/- 2 years, BMI 35.9 +/- 0.8 kg/m2) patients enrolled in the Shared Care programme (SC) were matched to 81 female and 20 male (age: 45.8 +/- 1.1 years, BMI 35.7 +/- 0.4 kg/m2) patients enrolled in a hospital based programme (MOS). MAIN OUTCOME MEASURES: Relative and absolute weight loss and retention rate were compared between the programmes at 10 and 26 weeks. Food habits were assessed at enrolment and week 10 of the programme in the SC group by a Food Habits Questionnaire and cognitive restraint, disinhibition and hunger were assessed by the Eating Inventory Questionnaire. RESULTS: Shared Care patients (n = 28) lost significantly more weight than the MOS patients (n = 60) (SC 4.8 +/- 0.6 kg and MOS 2.6 +/- 0.4 kg; p = 0.0016) over the 10 weeks of the programme. At 26 weeks both groups demonstrated a 5 kg weight loss. There was a significant improvement in food habits, and cognitive restraint, disinhibition and hunger over the 10 weeks of the programme in the SC group. Patient satisfaction was reflected in a better retention rate at 26 weeks by the Shared Care group. CONCLUSION: The study demonstrated that the obese patient managed in a shared care setting achieved better weight loss in the short term and attrition was lower in the longer term than a similar patient attending a specialist service based in a hospital.

Adult↗

PubMed1996

The effects of the inhibition of fatty acid oxidation on pyruvate dehydrogenase complex activity in tissues of lean and obese mice.

OBJECTIVE: To investigate the effects of an acute dose of the fatty acid oxidation inhibitor, Etomoxir, on the activity of the pyruvate dehydrogenase complex (PDHC) in different tissues in lean and obese mice. DESIGN: An acute dose of Etomoxir was given to mice in which obesity had been induced by an injection of gold thioglucose and to age-matched controls. The effects of time, dose and nutritional state were studied. MEASUREMENTS: PDHC activity in heart, quadricaps muscle, liver and white adipose tissue, glycogen content of liver and quadricaps muscle, serum glucose and insulin were measured in fed and fasted animals and in fasted animals after the ingestion of a glucose load. RESULTS: Etomoxir caused an increase in the activity of the active form of the PDHC (PDHCa) in the heart, liver and WAT of fed lean mice and in the heart and liver of fed obese mice. In fasted mice, increased PDHCa was seen in the heart of lean mice and in the liver of obese mice. Etomoxir increased the PDHC response to an oral glucose challenge in the liver and WAT of lean mice and in the liver of obese mice. Etomoxir had no effect on PDHCa in quadricaps muscle. Serum glucose levels were decreased in fasted mice with no change in the fed mice. Etomoxir decreased liver glycogen content in both fed and fasted animals and inhibited the accumulation of muscle glycogen following the glucose load. CONCLUSIONS: Acute inhibition of fatty acid oxidation results in tissue specific increases in PDHCa. Improvements in glucose oxidation in tissues other than skeletal muscle may contribute to the improved glucose tolerance seen following acute Etomoxir administration.

Adipose Tissue↗

PubMed1995

Tissue differences in the response of the pyruvate dehydrogenase complex to a glucose load during the development of obesity in gold-thioglucose-obese mice.

The activity of pyruvate dehydrogenase (PDHC), a key enzyme complex in the oxidative disposal of glucose, was measured after an oral glucose load in the heart, liver, quadriceps muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) of gold-thioglucose (GTG)-obese mice at different stages during the development of obesity and in age-matched controls. Significant responses to the glucose load were seen 30 min post-gavage in heart, WAT and BAT of control mice but no change was observed in quadriceps muscle. The increase in activity of the active form of PDHC (PDHCa) in response to glucose in heart was reduced 2 weeks after the induction of GTG-obesity with no response in 5 or 10 week obese mice. A 2-3-fold increase in the PDHCa response in both WAT and BAT of 2 week obese mice was absent in 5 and 10 week obese animals. Basal PDHCa activity in quadriceps muscle was increased in 2 week obese mice but subsequently returned to control levels as obesity progressed. The glucose load produced no change in the activity of PDHCa in quadriceps muscle of obese mice. These results demonstrate that changes in the capacity for oxidative glucose disposal in different tissues, as indicated by changes in PDHCa activity, may contribute to glucose-intolerance and insulin-resistance in GTG-obese mice and that the response of the PDHC to insulin during the development of obesity varies in different tissues.

Adipose Tissue↗

PubMed1995

High-fat feeding alters the response of rat PDH complex to acute changes in glucose and insulin.

The activity of the pyruvate dehydrogenase complex (PDHC) was studied in tissues of controls and insulin-resistant fat-fed rats (FFR) both in the fed state and in overnight fasted animals after the induction of short-term changes in plasma insulin by an intravenous glucose load. Significant responses by the PDHC to the glucose challenge were seen in heart and white adipose tissue (WAT) in controls with smaller changes in brown adipose tissue (BAT) and quadriceps muscle (QM) and no change in liver. Reduced PDHC responses and lower fed values were seen in heart and BAT of FFR. The response in WAT of FFR was prolonged with no change in the PDHC response in QM. Plasma nonesterified fatty acids (NEFA) were decreased in response to the glucose load with no differences between controls and FFR. Tissue triglyceride levels were higher in liver and QM but not heart of FFR. These results show differential tissue PDHC responses to short-term changes in plasma insulin. The decreased PDHC activity in some tissues of the fat-fed animals despite the lack of change in plasma NEFA, together with the triglyceride accumulation seen in some tissues but not others, suggests that local intracellular fatty acid metabolism is important in the regulation of intracellular glucose oxidation.

Animals↗

PubMed1995

Glucocorticoid deprivation alters in vivo glucose uptake by muscle and adipose tissues of GTG-obese mice.

The effect of 1 wk of glucocorticoid deprivation by surgical adrenalectomy (ADX) on tissue 2-deoxy(-)[U-14C]glucose (2-DG) uptake and hepatic glucose production (HGP) was assessed in conscious, catheterized mice 5 wk after the induction of obesity with gold thioglucose (GTG). Despite the prevailing hyperglycemia and hyperinsulinemia, glucose uptake by heart, quadriceps muscle, and interscapular brown adipose tissue (BAT) of GTG-obese mice was unchanged compared with controls, suggesting that the hyperglycemia of GTG-obese mice is able to compensate for the insulin resistance of these tissues. In contrast, epididymal white adipose tissue (WAT) of GTG-obese mice showed increased glucose uptake with hyperglycemia and hyperinsulinemia. ADX decreased the hyperglycemia and lowered the elevated glycogen content of the liver of GTG-obese mice. ADX reduced glucose uptake by heart and WAT of control and GTG-obese mice, consistent with the concomitant decrease in insulinemia. Glucose uptake by muscle of control and GTG-obese mice was not significantly decreased after ADX despite the decrease in insulin, and ADX increased glucose uptake by BAT of GTG-obese mice, suggesting increased sympathetically mediated thermogenesis in this tissue. HGP was increased in GTG-obese mice compared with controls, and ADX significantly reduced HGP in both GTG-obese and control mice. These results suggest that the improved glucose tolerance of ADX GTG-obese mice and ADX control mice is due to a decrease in HGP rather than an increase in peripheral glucose uptake.

Adipose Tissue↗

PubMed1995

Dexfenfluramine treatment of obesity: a double blind trial with post trial follow up.

OBJECTIVE: As successful weight management demands a long term approach, a better understanding of weight changes during and for significant periods after cessation of dexfenfluramine therapy is essential to the evaluation of the drug's effectiveness in clinical practice. This study aimed to investigate additional benefits to weight loss during 6 months treatment with dexfenfluramine in 60 patients enrolled in a weight loss programme. DESIGN: Sixty obese subjects (21 males; 39 females) were randomised to dexfenfluramine (15 mg twice daily) or placebo for six months. Fifty one (27 dexfenfluramine; 24 placebo) subjects completed the double blind, randomised, placebo controlled clinical trial. RESULTS: After a one month 'run in' phase and six months treatment, weight loss in the dexfenfluramine group was significantly greater than placebo, 9.7 +/- 1.1 kg vs 4.9 +/- 0.9 kg (mean +/- s.e.m.); P = 0.002. Reduction in body fat, 5.0 +/- 0.7 kg vs 1.0 +/- 0.9 kg; P = 0.002 and waist circumference, 10.5 +/- 1.9 cm vs 5.7 +/- 1.1 cm; P = 0.04 was also greater in the dexfenfluramine group. Despite significant weight loss, waist to hip ratio (WHR) did not change in either group. The dexfenfluramine group reported a significantly greater incidence of nausea, dry mouth and dizziness which tended to decrease as treatment progressed. No subjects withdrew due to drug induced side effects. Reduction in serum triglyceride levels and an increase in HDL cholesterol (in female subjects) in conjunction with a reduction in fasting insulin, collectively support an improved cardiovascular risk profile in the dexfenfluramine group. Despite significant weight loss, these risk factor measurements worsened in the placebo group. After cessation of dexfenfluramine therapy, there was a significantly greater weight regain indicating a loss of treatment effect. By 5 months after cessation of dexfenfluramine, the treatment effect was negated with weight loss in the dexfenfluramine (6.0 +/- 1.6 kg) and placebo (6.2 +/- 1.3 kg) group, similar. CONCLUSION: The results of this study support the longer term use of dexfenfluramine therapy for patients with chronic obesity.

Adolescent↗

PubMed1994

Effect of adrenalectomy on glucose tolerance and lipid metabolism in gold-thioglucose obese mice.

The effect of adrenalectomy (ADX) on body weight, lipogenesis, and glucose tolerance was investigated in mice made obese by a single intraperitoneal injection of gold-thioglucose (GTG). Five weeks after ADX the weight of GTG-obese mice was significantly decreased (GTG-obese+sham-ADX: 39.8 +/- 0.8 g; GTG-obese+ADX: 27.6 +/- 1.1 g; P < 0.05). ADX also reduced serum glucose (GTG-obese+sham-ADX: 16.5 +/- 0.6 mmol/l; GTG-obese+ADX: 10.8 +/- 0.5 mmol/l; P < 0.05) and serum insulin concentrations (GTG-obese+sham-ADX: 197 +/- 36 microU/ml; GTG-obese+ADX: 38 +/- 7 microU/ml; P < 0.05) of fed GTG-obese mice and greatly improved glucose tolerance. ADX lowered liver glycogen content and reduced the fatty acid content of liver, epididymal white adipose tissue (WAT), and interscapular brown adipose tissue (BAT) of fed GTG-obese mice. Lipid synthesis in liver and WAT of GTG-obese mice was decreased by ADX, but lipogenesis in BAT was increased, possibly to provide substrate for increased thermogenesis in this tissue. Effects of ADX on metabolism were not confined to GTG-injected mice, as ADX also reduced body weight and altered the glucose tolerance of age-matched control mice. ADX increased lipid synthesis in liver, WAT, and BAT of fed control mice without an increase in lipid deposition, indicating that there was increased lipid turnover in these lipogenic tissues of ADX mice. ADX reduced the fasting blood glucose concentration of both control and GTG-obese mice to a level below that of sham-ADX control mice (sham-ADX control: 6.0 +/- 0.4 mM; ADX control: 2.9 +/- 0.5 mM; ADX GTG-obese: 3.3 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Changes in glycogen metabolism in liver of gold thioglucose injected mice during the development of obesity.

A study of glycogen metabolism in the liver has been carried out in gold thioglucose (GTG) injected mice during the development of obesity. In GTG obese mice, overt obesity, hyperglycaemia and hyperinsulinaemia had developed by 6 weeks after the injection of GTG. Beyond 6 weeks after GTG injection, the gain of body weight and increment in serum glucose and insulin levels with age in obese mice were not obvious when compared with those of age-matched control animals. The glycogen concentration, total glycogen storage, activity of glycogen synthase R and activity of phosphorylase a in the liver from GTG obese mice were significantly greater than those in lean mice from 2-4 weeks after GTG injection and remained higher thereafter. These results demonstrate that the increased liver glycogen storage and increased activity of glycogen synthase and phosphorylase occur early in the development of obesity and at a similar time to previously reported increases in pyruvate dehydrogenase activity (Caterson et al. (1987) Biochem. J. 243, 549-553) and lipid synthesis in liver (Cooney et al. (1989) Biochem. J. 259, 651-657). The emergence of these abnormalities in glycogen metabolism early in the development of obesity may contribute to the establishment of glucose intolerance and insulin resistance in this model of obesity which became apparent at approximately the same time after GTG injection.

Analysis of Variance↗

PubMed1994

Tissue [1-14C] 2-deoxyglucose metabolism in the gold thioglucose obese mouse: effects of 'dieting'.

Glucose uptake into heart and skeletal muscle and white and brown adipose tissue is reduced in mice with gold thioglucose-induced obesity. After acute dieting (40% of lean control uptake) for 18 days, glucose uptake into tissues remains low despite consistently elevated serum insulin levels. This reduced glucose uptake may be a consequence of the raised serum fatty acid levels produced by dieting. When the reduced weight obese mice are pair-fed with lean controls, they gain weight. Glucose uptake into both muscle and adipose tissues is markedly increased, and the insulin resistance of both previous obesity and recent relative starvation is rapidly overcome at the level of the glucose uptake, but serum insulin levels and insulin secretion from islets of Langerhans isolated from these animals remain high. To maintain reduced weight, previously obese animals were fed 80% of lean control intake. In this situation, glucose uptake into the four tissues studied remained reduced (compared to lean controls), consistent with relative starvation. While tissue glucose uptake increases after dieting and re-feeding of obese animals, serum insulin levels remain high, indicating persistence of a degree of insulin resistance. Reduced-weight obese animals are energy-efficient in that they gain excess weight on the control intake.

Adipose Tissue↗

PubMed1994

The prevalence of obstructive sleep apnoea in an obese female population.

Obstructive sleep apnoea (OSA) has been estimated to affect between 1 and 4% of the total population. OSA may be more frequent among women than studies based on subjects presenting for treatment would indicate. The aim of this study was to determine the prevalence of OSA in an obese female population (BMI > 30 kg/m2, age > 18 years) who presented to a hospital-based obesity clinic. The women were screened by an overnight ambulatory sleep study (MESAM) to detect OSA. Subjective sleep quality and sleep disturbance were assessed by a 19-item questionnaire, the Pittsburg sleep quality index (PSQI). From a population of 108 women, 29 were screened by MESAM. OSA was determined on the basis of respiratory disturbance index (RDI). The prevalence of OSA, defined as five or more respiratory disturbances per hour, was 37.9%. The mean age of the women was 43.6 +/- 2.57 years (mean +/- s.e.m.) and they had a mean BMI of 40.7 +/- 1.40 kg/m2. There was a significant positive correlation for RDI and BMI (r = 0.71; P < 0.001). Our findings indicate that over one third of women had OSA, yet they did not complain of symptoms even though the PSQI questionnaire indicated that they were poor sleepers. Non-specific symptomatology of OSA may be important diagnostically, particularly in women, and obese women should be considered at risk of OSA.

Adult↗

PubMed1993

Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice.

The diurnal pattern of the activity of the pyruvate dehydrogenase complex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG)-obese mice and age-matched controls. The diurnal pattern of lipogenesis was also measured in the liver. Both lean and obese mice had one main eating period, from 20:00 to 24:00 h. Eating produced no change in serum glucose of control mice but there was a significant rise in serum insulin and triacylglycerols. There was also a 3-fold increase in cardiac PDHC activity and a 3-fold increase in hepatic lipogenesis in the control mice, but little change in hepatic PDHC activity. GTG-obese mice were hyperglycaemic, hyperinsulinaemic and hypertriglyceridaemic at all times studied, with significant increases in these parameters being seen in response to eating. Eating produced little change in cardiac PDHC activity, but there was a 5-fold increase in hepatic PDHC activity, paralleled by a 10-fold increase in hepatic lipogenesis. Hepatic PDHC activity was significantly higher in GTG-obese mice at all times except 16:00 h. The simultaneous rise of hepatic PDHC activity, lipogenesis and serum triacylglycerols in GTG-obese mice suggests an increased utilization of glucose for lipogenesis. The lack of change in heart PDHC activity in GTG-obese mice over 24 h suggests that a general decrease in PDHC activity may contribute to the development of the glucose intolerance and insulin resistance of obesity and non-insulin-dependent diabetes. However, it appears that a different level of metabolic control allows hepatic PDHC activity of the same obese animals to increase in response to hyperinsulinaemia and contribute to the higher rates of lipogenesis seen in obese mice.

Animals↗

PubMed1993

In vivo insulin sensitivity of the pyruvate dehydrogenase complex in tissues of the rat.

Activity of the insulin-activated pyruvate dehydrogenase complex (PDHC) is necessary for the complete oxidation of glucose to carbon dioxide or the conversion of glucose to fatty acids in lipogenic tissues. To determine the in vivo insulin sensitivity of PDHC activity in rat tissues, we measured the amount of PDHC in the active form in heart, diaphragm, red quadriceps, white adipose tissue (WAT), and brown adipose tissue (BAT) of rats exposed to five different circulating insulin concentrations under euglycemic clamp conditions. PDHC was measured in mitochondrial extracts of tissues rapidly dissected from rats in the starved state or after euglycemic clamp (4 mM) at insulin infusion rates of 0, 0.125, 0.25, and 2.0 U.kg-1.h-1. Increasing the insulin concentration increased the PDHC activity in all tissues, but the magnitude of this activation was different in different tissues (heart: 3.5-fold; diaphragm: 2.5-fold; red quadriceps: 1.8-fold; WAT: 3.4-fold; and BAT: 10.5-fold). Calculation of the half-maximal effective dose (ED50) for the activation of PDHC produced values that were similar in all tissues (heart: 112 pM; diaphragm: 108 pM; red quadriceps: 146 pM; WAT: 120 pM; and BAT: 118 pM). The insulin sensitivity of PDHC in these tissues correlated particularly well with the ED50 for the insulin effect of decreasing circulating nonesterified fatty acids (NEFA; 122 pM). The differences in the magnitude of the effect of increasing insulin on PDHC activity implies a tissue difference in the requirement for an increased capacity for glucose oxidation after insulin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1993

Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats.

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Liver and peripheral tissue glycogen metabolism in obese mice: effect of a mixed meal.

Glycogen metabolism in the liver, skeletal muscle, cardiac muscle, and white adipose tissue was studied in gold thioglucose (GTG) obese mice after fasting and during refeeding. Prolonged (48 h) fasted control and GTG mice were refed with standard laboratory diet for 24 h. During fasting and refeeding, the changes in glycogen content and the activity of glycogen synthase I and R and phosphorylase alpha in the liver were similar in lean and GTG mice. However, the glycogen storage in the livers from GTG mice was always greater than that in lean animals. In GTG mice the activity of liver glycogen synthase I and R was significantly higher than that in lean animals 3 and 6 h after refeeding. The activity of liver phosphorylase alpha in GTG mice was higher than that in lean mice after refeeding. There were no significant differences in the glycogen content of white adipose tissue, cardiac muscle, and skeletal muscle from lean and GTG mice during the entire study. The results of this study suggest that increased glycogen storage in the liver is a major alteration in nonoxidative glucose metabolism and contributes to the development of insulin resistance and glucose intolerance in GTG obese mice.

Analysis of Variance↗

PubMed1993

Insulin response to an intravenous glucose load during development of obesity in gold thioglucose-injected mice.

The insulin secretory response to an intravenous glucose load was examined in chronically catheterized, conscious mice 2, 5, and 10 wk after induction of obesity by a single injection of gold thioglucose. At 2 wk after administration of gold thioglucose, a significant increase in both the insulinemia and incremental area under the curve of insulin release after intravenous glucose were observed (incremental area under the curve for 2-wk control mice, 852 +/- 54 min/pM; incremental area under the curve for 2-wk GTG-injected mice, 1140 +/- 114 min/pM; P < 0.05). At this stage, no significant difference existed in the glucose tolerance or body weight of control and gold thioglucose-injected mice. By 5 wk, the gold thioglucose-injected mice were approximately 33% heavier than their lean controls and showed a marked glucose intolerance. This was accompanied by overt hyperinsulinemia in both the basal state and also in response to an intravenous glucose bolus as indicated by the increase in the incremental area under the curve of insulin (5-wk control mice, 816 +/- 114 min/pM; 5-wk gold thioglucose-injected mice, 1374 +/- 156 min/pM; P < 0.05). At 10 wk after gold thioglucose administration, body weight and the degree of glucose intolerance were increased. Although 10-wk gold thioglucose-injected mice showed basal hyperinsulinemia, an intravenous glucose bolus elicited a smaller insulin secretory response than that observed in the age-matched lean control animals (10-wk control mice, 672 +/- 54 min/pM; 10-wk gold-thioglucose-injected mice 186 +/- 42 min/pM; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Severe obesity: the use of very low energy diets or standard kilojoule restriction diets.

OBJECTIVES: To determine the efficacy of two dietary therapies in both the short term (hospitalisation) and the longer term treatment of severe obesity. DESIGN: A descriptive study of two patient groups with obesity defined by a body mass index of greater than 30 kg/m2. SETTING: A multidisciplinary weight control program in a tertiary care hospital. PATIENTS: All admissions to hospital of patients on the weight control program for initiation of weight loss during a period of 48 months. INTERVENTION: A standard kilojoule reduction regimen or the use of complete, followed by partial, long term meal substitution with a very low energy liquid diet (VLED), coupled with an exercise and a behavioural modification program. OUTCOME MEASURES: Weight loss during and after hospitalisation was measured in both dietary regimen groups. RESULTS: Both diets induced weight loss in hospital. Men prescribed VLED lost significantly more weight, 8.3 +/- 0.8 kg (mean +/- SEM) than women prescribed this diet (5.5 +/- 0.5 kg) or standard kilojoule restriction (5.1 +/- 0.8 kg). CONCLUSIONS: VLED and standard kilojoule restriction are both effective for the treatment of severe obesity, particularly in a controlled environment (hospitalisation). In the longer term, VLED is an effective method of maintaining weight loss. Lack of continuing weight loss may reflect the patients who were initially placed on this regimen--small eaters with a presumed high metabolic efficiency.

Adult↗

PubMed1992

The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice.

The responses of hepatic glycogen synthase and phosphorylase to fasting and refeeding were assessed as part of an investigation into possible sites of insulin resistance in gold thioglucose (GTG) obese mice. The active forms glycogen synthase and phosphorylase (synthase I and phosphorylase a) and the total activity of these enzymes were estimated in lean and GTG mice over 48 h of food deprivation, and for 120 min after glucose gavage (1 g/kg wt). In lean mice there was a maximal reduction in hepatic glycogen content after 12 h of starvation and the activity of phosphorylase a decreased from 23.8 +/- 1.9 to 6.8 +/- 0.7 mumol/g protein/min. These changes were accompanied by an increase in the activity of synthase I (from 0.14 +/- 0.01 to 0.46 +/- 0.04 mumol/g protein/min). In obese mice, similar changes in enzyme activity occurred after 48 h of starvation. These changes were accompanied by a significant reduction in the hyperinsulinemia and hyperglycemia of the GTG mice. After glucose gavage in both lean and obese mice, the activity of synthase I further increased over the first 30 min and declined thereafter. The activity of phosphorylase a increased progressively after refeeding. Results from this study suggest that despite increased hepatic glycogen deposition, the responses of glycogen synthase and phosphorylase, in livers of obese mice, to fasting and refeeding are similar to those of control mice even in the presence of insulin resistance.

Animals↗