The high-fat phenotype: is leptin involved in the adaptive response to a high fat (high energy) diet?

OBJECTIVE: To investigate physiological differences which could influence the balance between energy expenditure and energy intake, between habitual high-fat (HF) and low-fat (LF) consumers and the potential for weight gain. SUBJECTS: Ten HF and nine LF consumers, all young, lean males (% energy from fat 45.4 and 31.8, respectively). MEASUREMENTS: Habitual dietary variables (from the food frequency questionnaire, FFQ), body mass index (BMI), % body fat (% BF, measured by impedance), fasting concentrations of plasma leptin, glucose and triglycerides. RESULTS: HF and LF subjects (selected for their fat intake) did not differ significantly in BMI or % BF. HF subjects had significantly higher concentrations of plasma leptin and lower concentrations of plasma glucose than LF subjects. In all subjects, concentrations of fasting plasma leptin correlated significantly with BMI, % BF and fat mass; difference in leptin between groups remained significant when BMI and % BF were used as covariants. Leptin significantly correlated with dietary variables; particularly dietary fat (% energy and g) and inversely with dietary carbohydrate (% energy), but showed no correlation with dietary protein or total energy intake. CONCLUSION: Significant differences in concentrations of fasting plasma leptin have been observed between lean male HF and LF consumers. These findings suggest that the difference in leptin concentrations could be associated with a metabolic adaptation which could help to offset the weight inducing properties of high fat (high energy) diets.     

Hypolipidaemic effects of fenofibrate are not altered by mildronate-mediated normalization of carnitine concentration in rat liver

OBJECTIVE: To study the relationship between anatomic changes in the peripubertal female and sex hormonal maturation. STUDY DESIGN: Medical records were reviewed on virginal females whose first gynecologic examination occurred between ages 9 and 20 and who were examined at least twice by the same gynecologist. Speculum sizes at each visit were surrogate measures of circumferential hymenal elasticity, the anatomic change of interest. RESULTS: Mean ages at the two visits for the 35 patients were 14.6 and 16.7 years, respectively, with substantial overlap in ages between visits. Average Tanner breast and pubic hair stages and speculum sizes were greater at the second visit (P < .001). At first visit, age, Tanner breast and pubic hair stages, and time elapsed from menarche, thelarche and pubarche correlated positively with larger speculum sizes (P < .10). Change in speculum size between visits was associated with younger age and lower Tanner pubic hair stages at first visit and with increases between visits in age, body mass index and Tanner pubic hair stages. Larger changes were associated with shorter elapsed time between the first visit and menarche, thelarche and pubarche. CONCLUSION: Circumferential hymenal elasticity increases during adolescence. This anatomic change, the surrogate measure of which is specula diameter, can be used along with Tanner staging as a measure of physiologic maturity in adolescent women.     

Long-term effects of feeding high carbohydrate diet in pre-weaning period by gastrostomy: a new rat model for obesity

In the present study, we report the long-term metabolic consequences of feeding a milk substitute formula that is high in carbohydrate-derived calories during the suckling period. Male Sprague-Dawley rat pups were raised by gastrostomy on a high carbohydrate (HC) formula or a high fat (HF) formula (which mimicked rat milk composition in macronutrients) during the pre-weaning period (day 4 to 24). These rats were then weaned to a laboratory stock diet and subsequently challenged with a high sucrose diet to augment the development of obesity. The pups receiving the HC formula developed obesity in later life, even though there was no change in the body weight of this group compared to mother-fed (MF) controls or HF formula fed animals during the pre-weaning period. The HC rats were hyperinsulinemic and their growth rates were greater than MF rats starting at day 55. The lipogenic capacity of liver as well as adipose tissues (epididymal and omental) was higher in HC animals compared to MF control animals, as reflected by increases in two key lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase) and in vitro synthesis of lipids. An analysis of adipose tissue morphology in adult rats showed an increase in cell size in epididymal adipose tissue of HC rats compared to the MF group. However, there was no significant difference in cell size in omental adipose tissue between the MF and HC rats. The HF group behaved similarly to the MF control group in growth pattern and measured metabolic parameters.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The in vitro effect of prolactin (PRL) on protein phosphorylation in male guinea pig adrenal cortex has been studied. It was found that 60 min after addition of PRL (10 micrograms/ml) to slices of adrenocortical tissue the rate of protein phosphorylation increased considerably. Autoradiographic studies revealed that at least part of the proteins are substrates for protein kinase C, since their phosphorylation increased in the presence of specific activators of protein kinase C (Ca2+, diacylglycerol, phosphatidyl serine) in the incubation medium. The molecular masses of these proteins were 95, 93, 90, 12 and 10 kDa. In extracts of PRL-treated adrenocortical tissue phosphorylation of these proteins was especially well-pronounced. Addition of staurosporine (10 nM) during incubation of the slices abolished the PRL effect on protein phosphorylation without any effect on the rate of unstimulated phosphorylation. Taking into account the ability of isolated nuclei to respond to PRL by activation of protein kinase C, the time course of PRL stimulation of protein phosphorylation was studied using preparations of isolated nuclei. The maximal increase of 32P incorporation into the proteins from [gamma-32P]ATP was observed after 60 min. Staurosporine only slightly attenuated the PRL effect.     

The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride

OBJECTIVE: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals. DESIGN: Randomised crossover trial. SETTING: General community. SUBJECTS: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol/l and body mass index 26.0 (3.6) kg/m2. INTERVENTIONS: Participants completed two six week experimental periods during which they consumed either a traditional Western diet (36%, 18%, and 43% energy from total, saturated, and carbohydrate, respectively) or a low-saturated fat high-carbohydrate diet (22%, 6% and 59% energy from total, saturated, and carbohydrate, respectively). Dietary principles were reinforced regularly, but food choices were self-selected during each experimental period. MAIN OUTCOME MEASURES: Serum lipids, body weight and plasma fatty acids. RESULTS: Reported energy and nutrient intakes, plasma fatty acids, and a drop in weight from 79.1 (12.5) kg on the Western diet to 77.6 (12.0) kg on the high-carbohydrate diet (P < 0.001) confirmed a high level of compliance with experimental diets. Total and low density lipoprotein (LDL) cholesterol fell from 5.52 (1.04) mmol/l and 3.64 (0.88) mmol/l, respectively on the Western diet to 4.76 (1.10) mmol/l and 2.97 (0.94) mmol/l on the high-carbohydrate diet (P < 0.001). HDL cholesterol fell from 1.21 (0.27) mmol/l on the Western diet to 1.07 (0.23) mmol/l on the high-carbohydrate diet (P = 0.057), but the LDL:HDL cholesterol ratio improved from 3.17 (1.05) on the Western diet to 2.88 (0.97) on the high-carbohydrate diet (P = 0.004). Fasting triglyceride levels were unchanged throughout the study. CONCLUSIONS: Replacement of saturated fat with carbohydrate from grains, vegetables, legumes, and fruit reduces total and LDL cholesterol with only a minor effect on HDL cholesterol and triglyceride. It seems that when free living individuals change to a fibre rich high-carbohydrate diet appropriate food choices lead to a modest weight reduction. This may explain why the marked elevation of triglyceride and reduction of HDL cholesterol observed on strictly controlled high-carbohydrate diets may not occur when such diets are followed in practice.     

Independence of the effects of cholesterol and degree of saturation of the fat in the diet on serum cholesterol in man

The effect on the fasting serum lipid levels of adding daily 291 mg of cholesterol to diets containing 3 mg of cholesterol and equal fat content, but different fatty acid composition, was tested on 12 young men. The saturated diet provided 97 g/day of a staurated oil made up of 2 parts of palm oil and 1 part of coconut oil. The polyunsatured diet provided 97 g/day of safflower oil. The cholesterol was dissolved in 40 g of either oil incorporated into a spread. A similar spread, devoid of cholesterol, was fed during the cholesterol free periods. Duration of dietary periods was 14 days. Addition of cholesterol produced a mean elevation of serum cholesterol of 9 mg/dl (SE +/- 2.1) in the presence of the saturated diet, and of 8 mg/dl (SE +/- 1.6) in the presence of the polyunsaturated diet. Both cholesterol elevations were significant (P less than 0.01) but not significantly different from each other. Substitution of the saturated diet for the polyunsatured diet caused a significant elevation of serum cholesterol which was the same when the substitution was made in the presence or in the absence of added dietary cholesterol.     

The reinforcing effects of ethanol are altered by the endogenous neurosteroid, allopregnanolone

We examined the effect of systemic administration of the endogenously occurring progesterone metabolite, allopregnanolone, on oral self-administration of ethanol by male rats. Rats were trained to perform an operant response for presentation of 0.1 ml of a solution of 10% ethanol in water using the sucrose fading technique. After acquisition of stable lever-press responding on a fixed-ratio 4 schedule, subjects received subcutaneous injections of 1, 3, or 10 mg/kg of allopregnanolone, or vehicle, 20 min prior to the self-administration session. Pretreatment with 3 mg/kg, but not 1 or 10 mg/kg, increased the mean total number of lever press responses made to obtain ethanol, and therefore increased the mean total number of ethanol presentations. The number of responses and response rate were examined as a function of the number of "runs" within the 30-min session; a "run" was defined as a series of consecutive responses with an interresponse interval of <1 min. The increase in total responses after 3 mg/kg was due in part to an increased number of responses for the first run of the session, with no effect on response rates. However, the higher dose of 10 mg/kg decreased response rates within the first run. Thus, allopregnanolone alters ethanol-reinforced responding at concentrations lower than those that depress rates of responding. The effects of administration of the benzodiazepene, diazepam, were determined for comparison with those of the neurosteroid. The subcutaneous injection of 0.3, 1.0, or 3.0 mg/kg of diazepam did not produce any clear dose-dependent changes in measures of ethanol-reinforced operant responding, supporting the suggestion of differences in the contribution of the benzodiazepene and neurosteroid binding sites to GABA(A) receptor function. The results indicate that exogenous administration of allopregnanolone dose-dependently alters ethanol-reinforced operant responding, and suggest that this endogenously occurring neurosteroid could mediate some of the reinforcing effects of ethanol.     

The vesicular monoamine transporter, in contrast to the dopamine transporter, is not altered by chronic cocaine self-administration in the rat

Although much evidence suggests that the brain dopamine transporter (DAT) is susceptible to dopaminergic regulation, only limited information is available for the vesicular monoamine transporter (VMAT2). In the present investigation, we used a chronic, unlimited-access, cocaine self-administration paradigm to determine whether brain levels of VMAT2, as estimated using [3H]dihydrotetrabenazine (DTBZ) binding, are altered by chronic exposure to a dopamine uptake blocker. Previously, we showed that striatal and nucleus accumbens DAT levels, as estimated by [3H]WIN 35,428 and [3H]GBR 12,935 binding, are altered markedly using this animal model (Wilson et al., 1994). However, in sequential sections from the same animals, [3H]DTBZ binding was normal throughout the entire rostrocaudal extent of the basal ganglia (including striatum and nucleus accumbens), cerebral cortex, and diencephalon, as well as in midbrain and brainstem monoamine cell body regions, both on the last day of cocaine access and after 3 weeks of drug withdrawal. These data provide additional evidence that VMAT2, unlike DAT, is resistant to dopaminergic regulation.     

Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue

Leptin concentrations were measured in the serum of cycling, pregnant, and lactating Sprague-Dawley rats. Serum leptin concentrations did not vary significantly during the estrous cycle. In contrast, as gestation advanced, serum leptin concentrations increased significantly, p < 0.0001. Following delivery, leptin concentrations declined and remained stable during lactation. Leptin messenger ribonucleic acid (mRNA) was identified in the visceral adipose tissue and placenta of rats sacrificed on days 14 and 21 of pregnancy. The relative abundance of placental leptin mRNA increased approximately 4 to 5 fold from day 14 to 21 of gestation. The pattern of elevated leptin concentrations in the serum of late pregnant rats is similar to that reported in pregnant women, therefore the rat may be a useful model for the study of leptin during pregnancy. The increase in leptin in the serum of late pregnant rats, as well as an increase in placental mRNA, raises the possibility that leptin may serve a physiological role for the late parturient rat and/or its young.     

Treatment with CL 316,243, a beta 3-adrenoceptor agonist, reduces serum leptin in rats with diet- or aging-associated obesity, but not in Zucker rats with genetic (fa/fa) obesity

Discrete subaortic stenosis (DSS) accounts for 8 to 20% of all cases of congenital left ventricular outflow tract obstruction. There have been few scattered reports of left ventricular obstructive lesions occurring in immediate family members of patients with DSS. This is a report of four cases of DSS in one family: one brother with a fibrous ring, and two sisters and the son of one of the sisters with a fibrous membrane. The occurrence of multiple cases of DSS in this family suggests an autosomal dominant mode of inheritance.     

Methane output and lactation response in Holstein cattle with monensin or unsaturated fat added to the diet

We measured effects of continuous vs twice-daily feeding, the addition of unsaturated fat to the diet, and monensin on milk production, milk composition, feed intake, and CO2-methane production in four experiments in a herd of 88 to 109 milking Holsteins. Methane and CO2 production increased with twice-daily feeding, but the CO2:CH4 ratio remained unchanged. Soybean oil did not affect the milkfat percentages, but fatty acid composition was changed. All saturated fatty acids up to and including 16:0 decreased (P < .01), whereas 18:0 and trans 18:1 increased (P < .001). The 18:2 conjugated dienes also increased (P < .01) when the cows were fed soybean oil. Monensin addition to the diet at 24 ppm decreased methane production (P < .01); the CO2:CH4 ratios reached 15, milk production increased (P < .01), and milkfat percentage and total milkfat output decreased (P < .01), as did feed consumption, compared with cows fed diets without monensin (P < .05). Milk fatty acid composition showed evidence of depressed ruminal biohydrogenation: saturated fatty acids (P < .05) decreased and 18:1 increased (P < .001); most of the increase was seen in the trans 18:1 isomer. As with soybean oil feeding, addition of monensin also increased (P < .05) the concentration of conjugated dienes. The monensin feeding trial was repeated 161 d later with 88 cows, of which 67 received monensin in the diet in the first trial and 21 cows were newly freshened and had never received monensin. Methane production again decreased (P < .05), but this time the CO2:CH4 ratio did not change and all other monensin-related effects were absent. The ruminal microflora in the cows that had previously received monensin seemed to have undergone some adaptive changes and no longer responded as before.     

Divergent effects of short-term, very-low-calorie diet on insulin-like growth factor-I and insulin-like growth factor binding protein-3 serum concentrations in premenopausal women with obesity

Patients who have sustained alcohol-related injuries are frequently treated in departments of oral and maxillofacial surgery. Often, an alcohol intervention will not be possible in accident and emergency departments due to intoxication but, when attending out-patient clinics for follow-up, patients are usually sober. This presents a unique opportunity for encouraging patients to review their alcohol consumption at a time when their facial injury may make them more receptive to advice. This article reviews the convincing evidence of the effectiveness of advice and brief interventions designed to be incorporated into standard out-patient consultations and describes practical screening of patients for harmful drinking, the Stages of Change Model of behaviour change and motivational interviewing for facilitating behavioural change.     

Enhancement of host resistance to microbial infections in mice fed a high fat diet by Lactobacillus casei cells

This paper will describe issues arising from a National Mental Health Project funded programme. This programme which is currently operating in Victoria, aims to provide assertive outreach support to the families of clients who have a psychiatric disability with a forensic history, and to the clients themselves. The support offered to families and clients by the Epistle Post Release Service was provided on the basis that patients with a major mental illness are prone to stress-related breakdown. By addressing their needs in a community setting, together with the provision of psychoeducation, emotional support and practical assistance, anxiety levels are diminished in both families and clients with the result that relapse and reoffending rates are reduced.     

Effects of high fat diet and cholecystokinin receptor blockade on pancreatic growth and tumor initiation in the hamster

The mechanism by which high-fat diet potentiates pancreatic cancer is not known, but trophic hormones may be involved. In preliminary growth studies, hamsters fed a high fat diet (17.5% lard, 17.5% corn oil) for 14 days showed a 16.3% increase (P < 0.01) in pancreatic weight compared to controls on low fat diet (2.5% lard, 2.5% corn oil). A significant increase was also seen at 28 days. Similar increases were seen in pancreatic DNA (29%, P < 0.01) and pancreatic RNA (22%, P < 0.05) at 14 days. Plasma cholecystokinin (CCK) levels at 14 days were 2.5 fold higher in the animals fed high fat (P < 0.01). Infusion of the CCK antagonist MK329 (25 nmol/kg/h) completely abolished the increase in pancreatic weight, pancreatic DNA and pancreatic RNA. The effect of CCK receptor blockade during the initiation period of carcinogenesis was investigated in hamsters fed the same diets used in the growth studies. One hundred animals received a single injection of N-nitrosobis(2-oxopropyl)amine, (BOP, 20 mg/kg). Half of the hamsters in each diet group received a 2 week infusion of MK329 (25 nmol/kg/h), beginning 8 days before carcinogen administration. At the time of death, 55 weeks after carcinogen administration, non-fasting plasma CCK levels were 31% higher in the high fat fed hamsters than in the low fat fed animals (P < 0.01). The high-fat diet group had a 3-fold increase in total cancer incidence and a 5-fold increase in advanced lesions (adenocarcinomas). Tumor incidence and yield were not changed in either diet group by CCK-receptor blockade during the initiation period. Cholecystokinin appears to mediate the short-term trophic effect that high-fat feeding has on the pancreas. However, potentiation of pancreatic cancer by high-fat diet in the hamster cancer model does not appear to be influenced by endogenous cholecystokinin at the time of tumor induction.     

Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects

The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.