Effects of diet and obesity on body weight regulation during pregnancy and lactation in the rat

The effects of obesity level and cafeteria feeding were studied in rats during pregnancy and lactation. The non-fetal weight gain in pregnancy was three times greater with the cafeteria diet than with chow, indicating that fat deposition is not regulated at an optimal level during pregnancy. There was a strong negative correlation between postpartum weight and weight change during lactation. Obese rats were finicky in that their weight changes in lactation were exaggerated when the diet was changed between pregnancy and lactation. Pup growth rate was proportional to maternal energy intake but in this experiment not related to maternal protein, fat or carbohydrate intake. In obese rats switched to chow, intake was inadequate for normal pup growth. Thus, the weight gains in pregnancy are not regulated at a set level, and the weight change in lactation appears to compensate for the weight gain in pregnancy.     

Self-selection and the obese Zucker rat: the effect of dietary fat dilution

Adult female lean and obese Zucker rats were allowed to compose their own diets by giving them access to three macronutrient sources. After a baseline period, the fat source was serially diluted. In all, eight concentrations of fat were used. Dilution of the fat source promoted significant increases in the intake of fat by both lean and obese rats. The increased intake of fat was not simply compensatory in nature, but rather represented significant increases in fat consumption. These results suggest that the reported increased appetite for fat of the obese rat is not a unique trait of that genotype. Further, results from this experiment demonstrate that caloric and protein regulation mechanisms may not be controlling the intake of obese and lean rats as precisely as once believed.     

子宫内膜异位症大鼠妊娠、哺乳期异位内膜的观察

目的:对比观察子宫内膜异位症大鼠妊娠期、哺乳期在位与异位内膜的组织学差异。方法:雌性成熟SD大鼠,自体移植法造子宫内膜异位症模型,造模成功后以雌雄比例2:1与雄鼠同笼饲养,雌鼠阴道细胞涂片发现精子当天定为"孕鼠",于孕12d处死孕鼠7只,取其在位、异位内膜甲醛固定,石蜡包埋、切片。另7只待其自然分娩后哺乳20d后处死,取其在位及异位内膜,同法切片。结果:模型组大鼠妊娠期在位子宫内膜符合妊娠期改变,可见A-S现象及蜕膜组织,而所有妊娠期大鼠异位内膜仅见不同程度分泌现象。模型组大鼠哺乳期在位内膜呈增生期改变,而异位内膜发育较其在位子宫内膜迟,并呈现坏死趋势。结论:由于生长环境不同,异位内膜对各种内分泌激素的反应与在位子宫内膜相比存在敏感差异。妊娠、哺乳对子宫内膜异位症可起到良好的治疗作用。     

Effect of liquid and solid preloads on eating behavior of obese and normal persons

Although the obese are unresponsive to internal state and generally regulate their caloric intake poorly, recent studies suggest that the nature of the food may be important. An experiment was conducted to test the regulation of obese and normal weight humans after liquid or solid preloads of 200 or 600 calories. Normal subjects regulate in accordance with caloric preload on both the liquid and solid diets. Obese subjects regulate intake on the liquid diet and not on the solid diet.     

Caloric regulation in normal-weight men maintained on a palatable diet of concentional foods

The spontaneous food intake of six normal-weight male volunteers was measured for 24 days while the subjects were inpatients on a metabolic unit. They were fed a palatable diet of conventional foods and were kept unaware that their food intake was being measured. On days 7–18 the caloric content of their diet was covertly reduced by 25% by substituting aspartame-sweetened analogues for all menu items containing sucrose. Subjects did not alter their food intake for 3 days. Then between days 4–6 on the aspartame diet, they increased their intake to compensate for 40% of the missing calories. Food intake stabilized at 85% of baseline and remained the same for the rest of the 12-day dilution period. Subjects did not show a shift in either sweetened or unsweetened food choices while their diet was being diluted. In adjusting for the missing calories, they simply ate more of their customary diet. The replacement of sucrose by aspartame tended to curb the weight gain observed on the baseline diet.     

Effect of exercise on energy intake and eating patterns in lean and obese humans

Twelve obese and four lean subjects increased their energy expenditure by 100 kcal/day by cycling on a bicycle ergometer. The order of testing was alternated so that half of the subjects did exercise on the first three days and the remainder on the last three days. Ad lib energy intake was measured over six days using an automated food dispensing machine. The obese subjects ate 1196±517 kcal/day and the lean subjects ate 1162±301 kcal/day and showed no overall significant difference in energy intake or eating patterns. However, these obese subjects ate 18 kcal/day less and the lean subjects ate 155 kcal/day more during the exercise period. The difference in response confirms the hypothesis that lean subjects tend to regulate energy intake more accurately than obese subjects. Exercise increased the frequency of eating and drinking and decreased hunger and appetite for all subjects. There was a significantly greater decrease in hunger and appetite with exercise for the obese subjects. However, as there was no accompanying decrease in energy intake and some subjects had difficulty in completing the exercise, the value of small increases in voluntary exercise in the treatment of obesity is questioned.     

Effect of treadmill exercise on food intake and body weight in lean and obese rats

Body weight and food intake of lean and obese, male and female Osborne-Mendel rats following treadmill exercise were compared. Rats were assigned, separately by sex, to one of three diet groups; Group 1 was fed a low fat (10%) diet throughout the study, Group 2 was fed a high fat (55%) diet for 16 weeks and then switched to the low fat diet 1 week prior to exercise, and Group 3 was fed the high fat diet throughout the study. To control for differences in work output between the leanest and heaviest animals, exercise intensity was adjusted across groups such that all exercised rats had equivalent energy expenditure. After a 3 day training period, the exercise was successively increased over 8 days until a work output of 374.9J was reached. Relative to their respective controls, obese exercised males showed a reduction in body weight but no change in food intake. In contrast, exercised females showed no change in body weight or food intake, regardless of dietary condition.     

Effects of mother-litter separation and reunion on maternal aggression and pup mortality in lactating hamsters

This study examined the effects of a 24 hr mother-litter separation on maternal aggression and pup mortality in hamsters. There were four lactating groups tested for aggression in their home cages on days 5 and 15 postpartum: a group that was separated from their litters for 24 hr, a group that was not separated from their litters and two 24 hr separation groups in which the litters were returned 30 and 120 min prior to the aggression test. Nonreceptive, estrous cycling animals were used as controls (tested twice, 10 days apart) and as intruders. Measures of aggression recorded during the 10 min tests included the number of attacks, fights, chases and intruder retreats. Pup mortality was examined in the 4 lactating groups and in two additional non-tested groups, one of which was separated from their litters for 24 hr. Lactating hamsters initiated significantly higher levels of aggression than control animals. Mother-litter separation (24 hr) significantly decreased levels of aggression and these levels were restored when litters were replaced 30 and 120 min prior to aggression tests. There were few differences in levels of aggression between days 5 and 15 of lactation. Pup mortality was significantly greater between days 5–6 and 15–16 of lactation among those groups that were separated from their litters compared to those groups that were not separated. Significantly higher mortality levels were found between days 7 and 15 of lactation among the 2 groups in which pups were returned prior to the aggression test compared to all other groups.     

Dietary obesity in adult rats: Similarities to hypothalamic and human obesity syndromes

Normal adult female rats fed a variety of supermarket foods in addition to lab chow rapidly gained weight and became obese compared to rats fed only lab chow. Group housing the animals in an enriched environment did not alter the development of dietary obesity, but housing the rats in activity wheels reduced, although did not prevent, the obesity. The dietary obese rats did not normally defend their excessive weights since they were less willing to eat quinine diets, worked less for food, failed to increase their activity when deprived, and regained their weight at a slower rate following a fast than did controls. The similarity between this behavioral pattern and that displayed by hypothalamic obese rats and overweight humans is discussed.     

Role of gonadal hormones in diet selection and food utilization in female rats

Patterns of dietary self-selection were examined in ovariectomized and sham-operated female rats. Self-selection animals were offered separate dietary sources of protein, carbohydrate, and fat. Control animals were offered ground Purina Rodent Chow. Food intakes, water intakes, and body weights were measured daily for all animals. During a 19-day baseline period, selecting animals chose approximately one third of their daily caloric intake from each of the three diet sources. Following this baseline period, half of the self-selection animals and half of the control animals received bilateral ovariectomies, while the remaining animals in each diet group received sham-operations. Following ovariectomies, both self-selection and control animals significantly increased food intakes and rate of weight gains above baseline values. In contrast, sham-operated animals did not increase food intakes or rate of weight gain following surgery. When weight gain was calculated as a function of caloric intake, ovariectomized animals gained nearly twice as much weight per kilocalorie consumed as sham-operated animals. Ovariectomized animals showed no changes in diet selection after surgery, while sham-operated animals showed a slight decrease in the percentage protein selected. Differences between self-selection patterns in ovariectomized animals and in animals with other forms of experimentally-induced obesity suggest distinct metabolic patterns may underlie various forms of obesity.     

When identical twins differ: an analysis of intrapair differences in the spontaneous eating behavior and attitudes of free-living monozygotic twins

Heredity has been shown to have major influences on the body size and ingestive behaviors of humans. However, environment is also important as evidenced by the fact that even identical twins can differ in body size and nutrient intake. To investigate the relative influence of heredity and environment, differences between the body size and food intake of 110 identical adult twin pairs who were living independently were studied with a 7-day diet diary technique. Differences within twin pairs (intrapair differences) in diet density were related to differences in daily intakes, but not with body size differences. On the other hand, cognitive restraint and disinhibition were related to intrapair differences in body size, but not intake. The fact that there are important environmental and psychological factors that influence intake and body size, even in individuals who have identical genotypes, supports the recently proposed general model of intake regulation [de Castro JM, Plunkett S. A general model of intake regulation. Neurosci. Biobehav. Rev. 26 (5) (2002) 581-595].     

The connections of the medial preoptic region and maternal behavior in the rat

Female rats which are hysterectomized and ovariectomized on Day 16 of pregnancy and injected with estrogen show a short latency to onset of maternal behavior when presented with test pups 48 hrs later. In the present experiment, female rats were treated similarly except that on Day 16 of pregnancy they received knife cuts which severed either the lateral, anterior, dorsal, or posterior connections of the medial preoptic area (MPOA), or sham knife cuts. Severing the lateral connections of the MPOA severely disrupted materal behavior, while severing the dorsal or posterior connections of the MPOA produced either minor deficits or no deficits. Severing the anterior connections of the MPOA did produce large deficits in maternal behavior, but this was associated with hypoactivity and loss of body weight. Therefore, the maternal behavior deficits observed in the anterior cut group may have been a secondary effect of the knife cut. The results emphasize the importance of the lateral connections of the MPOA for maternal behavior.     

Pregnancy duration and fetal number: Effects on maternal behavior in rats

It was shown previously that in rats postpartum mothers are much more likely than pup sensitized virgin mothers to retrieve pups from a T-maze extension of their home cage. In the present experiment, the physiological basis of this difference was explored further by inducing maternal behavior (retrieving, crouching, licking) following hysterectomy-ovariectomy on Days 21, 16, and 10 of pregnancy. In general, the longer the duration of pregnancy, the shorter the latency to become maternal and the greater the propensity to retrieve pups from the T-maze. An additional group of Day 16 pregnancy terminated rats carrying six or fewer fetuses were not impaired with respect to onset of maternal behavior compared to their large-litter counterparts, but only a small percentage of these females retrieved in the T-maze. These findings suggest that both the late pregnancy estrogen surge and progesterone withdrawal after its peak and sustained secretion enhance maternal responsiveness and that T-maze pup retrieval (but not onset latency) may be additionally affected by the level of placental hormones.     

Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat

These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.     

Effect of physical activity on heart rate variability in normal weight, overweight and obese subjects: results from the SAPALDIA study

Many studies have demonstrated an association of both a sedentary lifestyle and a high body mass index (BMI) with greater risk for cardiovascular disease. Within the prospective SAPALDIA cohort (Swiss cohort Study on Air Pollution and Lung Diseases in Adults), we investigated whether regular exercise was protective against reduced heart rate variability (HRV), a clinically relevant predictor of cardiovascular morbidity and mortality, and whether adverse effects of obesity and weight gain on HRV were modified by regular exercise. Twenty-four-hour electrocardiograms were recorded in 1,712 randomly selected SAPALDIA participants aged >/=50, for whom BMI was assessed in the years 1991 and 2001-2003. Other examinations included an interview investigating health status (especially respiratory and cardiovascular health and health relevant behaviours including physical activity) and measurements of blood pressure, body height and weight. The association between regular physical activity and HRV and interactions with BMI and BMI change was assessed in multivariable linear regression analyses. Compared to sedentary obese subjects, SDNN (standard deviation of all RR intervals) was 14% (95% CI: 8-20%) higher in sedentary normal weight subjects; 19% (CI: 12-27%) higher in normal weight subjects exercising regularly >/=2 h/week; and 19% (CI: 11-28%) higher in obese subjects exercising regularly >/=2 h/week. Compared with sedentary subjects who gained weight, those who gained weight but did exercise regularly had a 13% higher SDNN (CI: 7-20%). Regular physical exercise has strong beneficial effects on cardiac autonomic nervous function and thus appears to offset the negative effect of obesity on HRV.     

Infertility: Effects of weight loss on the hormonal profile in obese, infertile women

This study was designed to investigate the effects of weightloss in obese, infertile women with special interest in changesof blood hormones, menstrual function and pregnancy rate. Bloodglucose, insulin, C-peptide and different steroid and pituitaryhormones during oral glucose loading were determined in a groupof 58 obese women with menstrual irregularities. Of the 58 women,35 took part in a weight-reducing programme lasting 32 ±14 weeks (mean ± SD) with a weight loss of 10.2 ±7.9 kg (therapy group). At the time of first oral glucose tolerancetesting, insulin resistance was a feature in 85% of the womenin the therapy group, and 22% were hyperandrogenaemic Weightloss resulted in a significant reduction in blood glucose, insulin,androstenedione, dihydrotestosterone and oestradiol concentrations.The pregnancy rate was 29% in this group and of them, 80% showedan improvement of their menstrual function. Thus, weight reductionis the appropriate treatment for women with obesity-relatedendocrine derangement, menstrual irregularity and infertility.     

Effects of age,sex, and prior body weight on the development of dietary obesity in adult rats

Adult male and female rats were fed either lab chow (Groups 2 and 3) or lab chow and an assortment of palatable supermarket foods (Group 1) during Days 1–60 of the experiment. All rats were maintained on only lab chow during Days 61–90. Group 1 and 3 rats were then given the supermarket diet during Days 91–150, while Group 2 rats continued on lab chow only. The rats fed the supermarket diet significantly more body weight than did the lab chow fed rats, and this dietary obesity was greater in the older rats (i.e., during the Days 91–150 of the experiment) than in the younger rats (Days 1–60). Male rats gained as much or more weight on the supermarket diet as did the females, but compared to the same-sexed chow fed rats females displayed greater weight gains than did males. Finally, during Days 91–150 Group 1 and 3 rats gained similar amounts of weight on the supermarket diet despite the fact that the Group 1 rats had previous experience with the diet and had been overweight as a result. The findings demonstrate that age and sex, but not prior experience with palatable foods and overweight, are important factors in the development of dietary obesity in adult rats. The similarity between dietary obesity and hypothalamic obesity with respect to these three factors is discussed.     

GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study

The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the γ-aminobutyric acid (GABA), a neurotransmitter involved in the regulation of food intake. The objective of the present study was to test for association between GAD2 single-nucleotide polymorphisms (SNPs) and eating behaviors, dietary intake and obesity in subjects (n = 873) from the Quebec Family Study (QFS). Energy and macronutrient intakes were measured using a 3-day dietary record and eating behaviors were assessed using the Three-Factor Eating Questionnaire (TFEQ). Six SNPs capturing about 90% of GAD2 gene variability were genotyped and tested for association with age- and BMI- adjusted phenotypes. No evidence of association was found in men. In women, a SNP (rs992990; c.61450 C > A) was associated with disinhibition (p = 0.028), emotional susceptibility to disinhibition (p = 0.0005) and susceptibility to hunger (p = 0.028). Another SNP (rs7908975; c.8473A > C) was associated with carbohydrate (p = 0.021) and lipid (p = 0.021) intakes, disinhibition (p = 0.011) and two of its subscales (emotional and situational susceptibility) as well as with avoidance of fattening foods (p = 0.036). Six-year weight gain was two times higher in women carrying the variants associated with eating behaviors: 4.2 kg (vs 2.1 kg in non-carriers) in A-allele carriers of c.61450 C > A (p = 0.038) and 4.9 kg (vs 2.5 kg in non-carriers) in C-allele carriers of c. 8473 A > C (p = 0.013). The results suggest a role for the GAD2 gene in determining food intake, eating behaviors and weight gain over time in women.     

Additive effects of leptin and topiramate in reducing fat deposition in lean and obese ob/ob mice

The objective of the present study was to investigate the effects of the antiepileptic drug topiramate (TPM) on components of energy balance in lean and obese (ob/ob) mice in the presence or absence of leptin. Lean and ob/ob mice infused with either leptin or phosphate-buffered saline were treated with TPM for 7 days. TPM was mixed into the diet and administered at a dose of 60 mg/kg/day, whereas leptin was infused at the rate of 100 microg/kg/day using osmotic minipumps, which were subcutaneously implanted in the interscapular region. Food intake and body weight were monitored throughout the study. Body composition was measured prior to and following treatment with TPM and leptin, using dual-energy X-ray absorptiometry (DEXA). Glucose (glucose oxidase method) and insulin (radioimmunoassay) were also determined. TPM and leptin significantly reduced body weight gain, food intake and body fat gain in obese mice. The effects of TPM and leptin on fat gain were also statistically significant in lean animals. There was no interaction of TPM and leptin on the energy balance variables, the effects of the two substances being additive instead. Leptin abrogated hyperinsulinemia in obese mutants whereas TPM did not alter insulin levels in either lean or obese mice. The combination of leptin and TPM led to the normalization of glucose levels in obese mice. Our study demonstrates an effect of TPM in leptin-deficient animals, which suggests that TPM does not require the presence of leptin to exert its effect. They also show that the effects of leptin and TPM can be additive. The treatment with leptin in ob/ob mice neither accentuated nor blunted the effect of TPM on energy balance.     

Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review

BackgroundTocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear.ObjectivesTo synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19.SourcesPubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed.ContentPublished data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding.ImplicationsAlthough the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.