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Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Supplementary data. Conflict of interest. Journal Article. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese?

A systematic review and meta-analysis of the evidence. Damian Best , Damian Best. Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, University of the West Indies, Queen Elizabeth Hospital, St. Michael, BB, Barbados.

A solution of deuterated endocannabinoids AEA-d4, 2-AG-d5, AA-d8, MAEA, oleoylethanolamide OEA -d2, palmitoylethanolamide PEA -d4 and 1-AG-d5, Cayman Chemicals, Ann Arbor, MI, USA in acetonitrile was added to the tissue along with μL of ice-cold 0.

Then, the samples were homogenized with a TissueLyser II Qiagen, Hilden, Germany for 60 s at 30 Hz. Subsequently, the samples were centrifuged for 10 min at g and 4°C.

The organic phase was removed and evaporated under a gentle stream of nitrogen at 37°C. The aqueous phase was further used for protein content determination.

The concentrations of internal standards, as well as the calibration curves, were set and tailored using test hypothalamic hippocampal and olfactory bulb tissues.

For protein quantification, the BCA method bicinchoninic acid assay was used and the measurements performed by using a FLUOstar Galaxy BMG Lab technologies. Anxiety-related behaviors were evaluated in handled animals with the elevated plus maze, at the 7—8th PN weeks adolescence period.

The elevated plus-maze Panlab, Barcelona, Spain consisted of a cross-shaped platform made of black and gray plastic. The platform was elevated 65 cm from the floor and had two opposing open arms 50 cm × 10 cm and two closed arms of the same size.

A central area of 10 cm connected all arms. The closed arms were fenced by cm high opaque walls. The light intensity was adjusted at lux in the open arms and 80 lux in the closed arms. The test was performed after 5 h from the beginning of the dark phase.

When the test started, each rat was placed in the central area facing one of the open arms and opposite to the experimenter position. Then, the animal was allowed to explore the maze freely for 5 min.

After this time, the rat was moved back to the home cage and the maze was cleaned. The number of open-arm and closed-arm entries and the percentage of time spent on open and closed arms were determined by a computer-controlled system recording the interruptions of infrared photo beams located along each arm.

Data were analyzed by using the MAZE soft software Panlab, Barcelona, Spain. Animals that fell off the maze during the test were excluded from the analysis. Locomotor activity and anxiety-related behavior were evaluated with the open field test in the 2 days following the elevated plus maze test.

The open field consisted of a square arena 80 cm × 80 cm and 40 cm high virtually divided into a peripheral zone and a central zone 40 cm × 40 cm.

It was made of plywood and was located in an experimental room illuminated with low light intensity 30 lux. The test was performed 5 h after the beginning of the dark phase.

Each rat was positioned in the center of the open field and was allowed to explore freely for 5 min. After this time, the rat was moved back to the home cage and the arena was cleaned.

The program calculated the percentage of time spent in the central area as well as the number of entries to the center zone, as an index of anxiety-like behavior. The chocolate preference test was performed at adolescence 8—9th PN weeks and adulthood 12—13th PN weeks.

At the beginning of the test, animals were single-housed in new cages provided with both types of food standard chow and the mixture of chocolates and water ad libitum. Food intake for both types of food and animal weight was determined 24 h after the beginning of the test.

Chocolate preference was calculated as the percentage of chocolate eaten over total food provided, a measure that was independent of the body weight of the animal and that only reflects food preference.

All data are expressed as mean ± SEM. Statistical analysis of results was performed by using the GraphPad Prism version 5. Weight gain over the time and caloric intake were analyzed by one-way repeated measures analysis of variance ANOVA.

Multiple comparisons were assessed by Bonferroni post hoc test. To assess the differences among groups on fertility-related parameters the chi-squared test was adopted. Results from the chocolate preference test were analyzed by two-way ANOVA with group control vs.

free-choice animals and age period used as variables. A p -value below 0. The evaluation of estrous cycle was performed daily during the 2 weeks before mating in order to detect alterations in regularity and duration of the different stages of the estrous cycle.

After the beginning of the experiment, 6 over 15 calorie-restricted dams suffered from prolonged diestrus or irregular cycle, whereas only 1 over 9 control rat dams did.

However, successful mating was finally achieved in both experimental groups. These results indicate that a moderate preconceptional caloric restriction do not affect fertility, despite the subtle changes observed during the estrous cycle and mating phase.

At mating, calorie-restricted dams tended to weigh less as compared to control dams mean weight control vs. restriction: Figure 2. Maternal weight gain during pregestation, gestation and lactation period. Cumulative weight gain g of control open triangles and restricted dams solid squares during pregestation A gestation B and lactation C.

Values are expressed as means ± SEM. Despite the change in body weight at the end of diet restriction, at PN0 calorie-restricted dams still tended to be leaner than controls mean weight and SEMs control vs.

restriction: ± Consequently, the percentage of increase in body weight between PN day 1 and 22 was higher for restricted dams than controls 5.

Figure 3. Maternal caloric intake during pregestation, gestation and lactation period. Cumulative caloric intake g of control open triangles and restricted dams solid squares during pregestation A gestation B and lactation C.

Control pups were born between GD 21 or 22, whereas all pups from calorie-restricted dams were born at GD 22 data not shown. All pups were born during the light phase. However, litter size tended to be lower in the diet restriction group Indeed, a significant decreased little size was found in female 6.

Figure 4. Hypothalamic endocannabinoid and NAE levels in male offspring at birth. A Anandamide AEA , B arachidonoylglycerol 2-AG , C Arachidonic acid AA , D oleoylethanolamide OEA , and E palmitoylethanolamide PEA in the hypothalamus of male offspring from control dams open bars and calorie-restricted dams solid bars at birth.

U Mann Whitney test showed a general propensity to reduced endocannabinoid levels in the hippocampus of offspring from calorie-restricted dams as compared to controls. No statistical differences between groups were found either in 2-AG or OEA levels Figures 5B,D , respectively.

Figure 5. Hippocampal endocannabinoid and NAE levels in male offspring at birth. A Anandamide AEA , B arachidonoylglycerol 2-AG , C Arachidonic acid AA , D oleoylethanolamide OEA , and E palmitoylethanolamide PEA in the hippocampus of male offspring from control dams open bars and calorie-restricted dams solid bars at birth.

U Mann Whitney test showed a slight tendency to decreased levels of AEA in the olfactory bulb of offspring from calorie-restricted dams Figure 6A.

No significant differences between groups were found in 2-AG, AA and PEA levels Figures 6B—D. The OEA values in olfactory bulb could not be reliably quantified due to interference of a peak corresponding to an isobaric structure of OEA data not shown.

Figure 6. Endocannabinoid and NAE levels in the olfactory bulb of male offspring at birth. A Anandamide AEA , B arachidonoylglycerol 2-AG , C Arachidonic acid AA and D palmitoylethanolamide PEA in the olfactory bulb of male offspring from control dams open bars and calorie-restricted dams solid bars at birth.

Values are expressed as mean ± SEM. Figure 7. Cumulative weight gain g of control group offspring open triangles and caloric restricted group offspring solid squares during lactation A and postweaning B period. Offspring adiposity, calculated as the percentage of the abdominal fat the sum of perirenal and perigonadal fat at 5th PN month, is shown in D : control offspring open bars vs.

caloric restricted offspring solid bars. These data are consistent with the increased body weight exhibited by these animals. Taking together, these results show that male offspring from preconceptional-gestational calorie-restricted dams presented higher body weight and weight gain and increased adiposity than controls in adulthood, despite the fact that caloric intake was not changed in these animals.

However, no differences were found either in the percentage of number of entries in the open arms or in the percentage of entries in the closed arms of the elevated plus maze data not shown.

Figure 8. Anxiety-related behaviors in male rat offspring. Anxiety-related responses were evaluated through the elevated plus maze test.

The percentage of time spent in open and closed arms of the elevated plus maze test is indicated in A,B respectively, and was calculated over the total test time s. In addition, the mean speed was not statistically different between groups data not shown.

These results suggest that alterations in the perinatal diet do not affect locomotor activity in the offspring. Two way ANOVA test performed with the chocolate preference test carried out in adolescence and adulthood, showed a statistically significant effect for the factor age period adolescence vs.

Thus, the preference for chocolate was increased over time in all groups. In contrast, no significant differences in the main effect of perinatal diet and no significant interaction between factors perinatal diet × age time were found.

However, the increment for chocolate preference by age period was slightly different between groups as revealed by Bonferroni multiple comparisons.

It is important to note that these findings were obtained using a model of moderate caloric restriction that does not affect fertility, but is sufficient to produce changes in the litter size and the body weight gain of dams Terry et al.

This is relevant because more severe diet restriction may have led to increased pre and postimplantational fetus loss.

In any case, the weight loss observed along preconceptional diet restriction might have produced an impact in the uterine glands that provide nutrition during the conceptional period and the first stages of pregnancy nutrients, a process known as histiotrophic nutrition Burton et al.

In addition, suboptimal nutrient conditions might have affected the embryos, through a process similar to that described in suboptimal in vitro culture in rodents, as we have recently shown Fernández-Gonzalez et al. Intriguingly, despite the decreased maternal weight gain during pregnancy, pups from calorie-restricted dams were not underweight at birth.

These findings are consistent with other studies showing that the weight at birth could be unaffected when caloric restriction is implemented in the early stages of pregnancy Sebert et al. This hypothesis is supported by the fact that offspring were born 2 days after switching the calorie-restricted dams to ad libitum feeding, suggesting that birth occurred only when fetuses reached the appropriate birth weight.

The endocannabinoid system is a relevant homeostatic network of signals controlling energy expenditure and metabolism Matias and Di Marzo, ; Bermudez-Silva et al. However, its role in developmental programming has not been studied in depth. Interestingly, we found that offspring from calorie-restricted mothers presented in general reduced levels of endocannabinoids and their precursor, AA, in hypothalamus and hippocampus and a similar tendency in the olfactory bulb, as compared to controls.

Reduced AA levels may be explained in part because AA n-6 derives from linoleic acid n-6 , which is an essential fatty acid obtained from dietetic sources.

Therefore, decreased availability of nutrients after a prolonged calorie-restricted maternal diet might have affected the levels of the precursor AA of the two predominant endocannabinoids AEA and 2-AG.

Conversely, reduced eCB levels, which are AA precursors as well, may also have determined in part the reduced levels of AA. In the hypothalamus, we detected a strong reduction in the level of the main endocannabinoids and AA. These results are in agreement with Matias et al.

However, in our experiments we detected more robust alterations in endocannabinoid and NAE levels likely because preconceptional diet restriction may induce more exacerbating effects in the offspring, as reported in both cohort studies Roseboom et al.

Consistently, we found reduced endocannabinoid levels in normoweight pups. However, the lack of association between endocannabinoid levels and pup weight is in disagreement with Matias et al. However, differently from Matias et al. Calorie-restricted rat dams tended to weigh less than controls at birth and their endocannabinoid levels might not have been restored to normal.

Thus, the endocannabinoid levels in new born rats might reflect the maternal status, due to the fact that long fatty acids can be transferred through the placenta and the fetus are not fully able to modify fatty acid structures Keimpema et al.

Future research will address these possibilities. Although the endocannabinoid system has received little attention in the context of nutritional programming, proteins interacting with endocannabinoids, such as leptin and brain-derived neurotrophic factor BDNF have been shown to be altered after maternal exposure to undernutrition Di Marzo et al.

For instance, after maternal undernutrition, alterations in the surge of leptin and BDNF levels during specific developmental stages have been associated to disruption in the development of the hypothalamic circuit and metabolic disorders later in life Bouret et al.

These data lead to hypothesize that the endocannabinoid system might be involved in the regulation of these processes as well. Indeed, during the prenatal and postnatal periods endocannabinoids levels reach a peak in concentration, which correlates with neurodevelopment processes occurring in these specific age stages Berrendero et al.

Moreover, alterations of endocannabinoid signaling by prenatal administration either of cannabinoid receptor agonists, such as THC Δ 9 -Tetrahydrocanabinol , or antagonists, is associated to impairment in neuronal activity, cortical connections and emotional behavior Rodríguez de Fonseca et al.

Importantly, our data suggest that prolonged prepregnancy-gestational undernutrition could have altered the normal fluctuations of endocannabinoid levels and thus, the establishment of functional circuitries involved in metabolism, ultimately leading to metabolic abnormalities later in life, as proposed by Keimpema et al.

Supporting this hypothesis, we have recently analyzed the expression of cannabinoid CB1 and CB2 receptors mRNA in the hypothalamus of adult offspring born from mothers exposed to pre- and gestational moderate caloric restriction and we have found a clear upregulation in the expression of both receptors, indicating long-term alterations in the offspring as result of maternal undernutrition Ramírez-López submitted.

Interestingly, although the levels of non-cannabinoid NAEs seem to be less influenced by diet Hansen and Diep, , we have found decreased levels of PEA in hypothalamus. PEA has been shown to exert anti-inflammatory Hoareau and Roche, and antiobesity effects Mattace Raso et al.

Taken into account this evidence, PEA level deregulation in early life may predispose to diseases associated to inflammation, such as obesity and metabolic syndrome Rana et al.

Further research should be pursued to corroborate these possibilities. We also found reductions in AEA levels and a strong tendency to decreased AA levels in hippocampus. It has been shown that circuits connecting hippocampus and hypothalamus are involved in the control of the hedonic aspects of eating Petrovich, and that hippocampal endocannabinoid levels can be altered according to different types of diet Rivera et al.

For instance, decreased levels of hippocampal endocannabinioids have been reported after exposing young animals to prolonged starvation Hanus et al. Moreover, we have recently reported decreased levels of hippocampal endocannabinoids after maternal exposure to a high-fat and low protein-containing diet Ramírez-López et al.

Taking into account that the endocannabinoids play an important role in the regulation of emotional processes and memory formation in this specific brain region Lutz et al. Finally, in the olfactory bulb, another brain structure involved in the regulation of metabolism and feeding behavior, we only found a tendency towards decreased AEA levels, similarly to that found in the hippocampus and hypothalamus.

Although these modifications were subtle, they still could have led to alterations in metabolism and feeding behavior later in life, considering the role of endocannabinoid signaling in odor perception and food intake Soria-Gómez et al.

Future studies are necessary to confirm these speculations. Although offspring were weaned on standard chow diet, male offspring form calorie-restricted dams started to gain more weight as compared to controls at the beginning of adulthood and exhibited overweight starting from the 15th PN week.

Increased weight was accompanied by augmented abdominal adiposity, although caloric intake was not changed in these animals. These long-lasting effects suggest that altered endocannabinoid levels, and presumably signaling, might be associated with inadequate wiring, which could directly trigger a pathological state.

Our findings are consistent with other studies showing similar alterations in offspring exposed to a maternal caloric restriction and weaned on a normocaloric diet Desai et al. Moreover, these effects have been shown either in offspring that were underweight Desai et al.

Interestingly, adult obesity in previously undernourished fetus has been associated to early catch-up growth Eriksson et al. Although we do not show direct evidence of early catch-up growth in calorie-restricted offspring, the fact that they were born normoweight and displayed increased weight gain during the first days of life suggests that these animals may be underweight during the fetal period but may have recovered at the end of the nutritional insult when dams were switched to normal diet.

Therefore, normal weight at birth may result from an accelerated catch-up growth, as similarly reported in animal models of maternal caloric restriction Desai et al. On the other hand, obesity in offspring exposed to maternal undernutrition has been also associated to hyperphagia Vickers et al.

However, our animals did not display modifications in the caloric intake relative to body weight consistent with the evidence that undernutrition in early life does not necessarily alter food intake Yura et al. Indeed, it has been reported that once offspring from animal models of maternal caloric restriction reach the same body weight as controls, their hyperphagic behavior ends Lukaszewski et al.

Under this framework, the increased body weight could be also explained by a reduction in energy expenditure linked to deregulation in endocannabinoid levels during early life, in accordance to the role of these bioactive lipids in food intake, energy balance and energy expenditure Matias and Di Marzo, ; Bermudez-Silva et al.

To explain the increased adiposity found in the adult offspring from calorie-restricted dams, additional mechanisms have been proposed. For instance, inadequate nutritional conditions in early life induce upregulation of adipogenic signaling pathways, increased expression of genes involved in adipocyte differentiation Guan et al.

Interestingly, the endocannabinoid system has been involved in adipogenesis and fat accumulation Matias and Di Marzo, However, the role of the endocannabinoid system in perinatal programming has not been elucidated yet and, in the current study, we have not addressed the potential impact of maternal diet restriction on endocannabinoid signaling alterations in the periphery, such as liver, muscle or adipose tissue.

However, recent preliminary data obtained using this model indicates changes in the expression of the enzymes controlling production and degradation of endocannabinoids in these peripheral tissues in adult offspring, suggesting that the observed alteration at birth might extend to the adulthood Ramírez-López submitted.

Further investigation are required to address these possibilities. Because of the importance of the long-term consequences of maternal undernutrition, we also explored the behavioral phenotype of adult offspring born from calorie-restricted dams. We have observed enhanced anxiety-related responses in adolescence, as measured by the elevated plus maze test, as previously described in humans Nomura et al.

In addition, make sure you record what you eat in an online food journal like Cronometer , at least in the beginning of your weight loss process.

Tracking your diet will help you ensure that you continue to reach your daily recommended nutrient intakes. When it comes to long-term weight loss, patience is key. Instead, opt for diets that are focused on diet quality and encourage you to make sustainable lifestyle changes.

In order to lose weight, you need to eat fewer calories than you burn. Here are 35 simple but highly effective ways to cut lots of calories. Calories matter, but counting them is not at all necessary to lose weight.

Here are 7 scientifically proven ways to lose fat on "autopilot. Yo-yo dieting is the pattern of losing weight, regaining it and then dieting again.

This article examines 10 reasons why yo-yo dieting is bad for you. When limiting your calorie intake, it's important to choose nutritious low-calorie foods. Here are 42 healthy foods that are very low in calories. Discover which diet is best for managing your diabetes.

Getting enough fiber is crucial to overall gut health. Let's look at some easy ways to get more into your diet:. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect.

Nutrition Evidence Based 5 Ways Restricting Calories Can Be Harmful. By Alina Petre, MS, RD NL — Updated on January 30, How we vet brands and products Healthline only shows you brands and products that we stand behind.

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Was this helpful? People trying to lose weight often restrict the number of calories they eat. Your Calorie Needs, Explained. Your body requires calories to function and uses them to sustain three main processes 1 : Basal metabolic rate BMR : This refers to the number of calories needed to cover your basic functions, including the proper functioning of your brain, kidneys, heart, lungs and nervous system.

Digestion: Your body uses a certain number of calories to digest and metabolize the foods you eat. This is also known as the thermic effect of food TEF. Physical activity: This refers to the number of calories needed to fuel your everyday tasks and workouts.

However, restricting calories too much may harm your health in the following 5 ways. It Can Lower Your Metabolism. Summary: Severely restricting your calories can decrease your metabolism and cause you to lose muscle mass.

Improve cognitive processing Best, Restrictio Avenell, Siladitya Bhattacharya, How caloric restriction and fertility are weight-loss interventions for caloriic fertility in caloric restriction and fertility and men who restrictin overweight fettility obese? The prevalence of obesity is increasing worldwide, with a corresponding increase in overweight and obese patients referred with infertility. This systematic review aimed to determine whether non-surgical weight reduction strategies result in an improvement in reproductive parameters affected by obesity, e. delayed time to pregnancy, oligozoospermia and azoospermia. No prior reviews have examined this within the general fertility population, or in both sexes. An electronic search of MEDLINE, EMBASE and the Cochrane Library was performed for studies between January and March Restricting calories in Muscle development endurance nearing the end of caloric restriction and fertility fretility years may prolong fertility and reduce chromosomal Body density index in offspring, research published caloric restriction and fertility the Proceedings of the National Restroction of Sciences tertility. A strategy caloric restriction and fertility has been shown to caloriv age-related health problems calodic several restricgion studies may also combat a caloric restriction and fertility cause of caloric restriction and fertility infertility restrictlon birth defects. Investigators from Massachusetts General Hospital MGH have shown aand restricting the caloric intake eestriction adult female mice prevents a spectrum of abnormalities, such as extra or missing copies of chromosomes, that arise more frequently in egg cells of aging female mammals. Their report appears in the online Early Edition of the Proceedings of the National Academy of Sciences USA. Many studies have found that animals whose food intake is restricted but still sufficient to avoid malnutrition live longer and show fewer signs of aging than do animals given access to as much food as they want. The long-term effects of a caloric restriction diet in humans are being investigated in ongoing studies, but some health improvements, including reductions in cholesterol levels and other cardiovascular risk factors, have already been reported. An earlier study found that female mice maintained on a caloric restriction diet during most of their adulthood maintained their fertility into very advanced ages, even after being allowed to resume free feeding.