Search

The recent identification of brown adipose tissue in adult humans offers a new strategy to increase energy expenditure to treat obesity and associated metabolic disease. While white adipose tissue (WAT) is primarily for energy storage, brown adipose tissue (BAT) is a thermogenic organ that increases energy expenditure to generate heat. BAT is activated upon cold exposure and improves insulin sensitivity and lipid clearance, highlighting its beneficial role in metabolic health in humans. This review provides an overview of BAT physiology in conditions of overnutrition (obesity and associated metabolic disease), undernutrition and in conditions of altered fat distribution such as lipodystrophy. We review the impact of exercise, dietary macronutrients and bioactive compounds on BAT activity. Finally, we discuss the therapeutic potential of dietary manipulations or supplementation to increase energy expenditure and BAT thermogenesis. We conclude that chronic nutritional interventions may represent a useful nonpharmacological means to enhance BAT mass and activity to aid weight loss and/or improve metabolic health.

Purpose of Review: This manuscript reviews evidence collected during COVID-19 pandemic and provides information on the impact of body composition on severity and outcomes of the disease, analysing methods used for body composition assessment. Malnutrition-screening tools will also be discussed to screen and diagnose the patients at higher risk of COVID-19 severity and related worse outcomes., Recent Findings: COVID-19 can occur in a wide range of presentation, from asymptomatic to severe forms. Among the major risk factors for worse severity, overnutrition, undernutrition and body composition play a role in the ability to respond to SARS-CoV-2 infection. Excess fat accumulation (i.e. obesity) or lean mass loss and functionality (i.e. sarcopenia) or a combination of both (i.e. sarcopenic obesity) can affect whole-body functioning. These body composition alterations in the short-term can influence susceptibility and immunological responses to the virus, inflammatory reaction, metabolic and respiratory distress, while in the long-term can modulate disease outcomes, namely length of stay, time required for recovery, risk of ICU-acquired weakness and long-term disabilities, and potentially increase the risk of death., Summary: Individuals with malnutrition, sarcopenia, obesity, sarcopenic obesity and older adults with abnormal body composition or malnutrition risk may require tailored medical nutrition therapy to improve short and long-term COVID-19 outcomes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.

The aim was to test the hypothesis that prenatal under- and overnutrition in late gestation can program small intestinal (SI) growth, angiogenesis, and endocrine function to predispose for a hyperabsorptive state, thereby increasing the susceptibility to the adverse effects of an early postnatal obesogenic diet. Twin-pregnant ewes were exposed to adequate (NORM), LOW (50% of NORM), or HIGH (150% energy and 110% protein of NORM) diets through the last trimester (term ~147 days). From 3 days to 6 months of age, their lambs were fed either a moderate (CONV) or a high-carbohydrate high-fat (HCHF) diet. At 6 months of age, responses in plasma metabolites and insulin to refeeding after fasting were determined and then different segments of the SI were sampled at autopsy. Prenatal overnutrition impacts were most abundant in the duodenum where HIGH had increased villus amplification factor and lowered villi thickness with increased IRS-1 and reduced GH-R expressions. In jejunum, HIGH lambs had an increased expression of Lactate gene and amplified when exposed to HCHF postnatally. Specifically, in LOW, sensitivity to HCHF was affected in ileum. Thus, the mismatching LOW-HCHF nutrition increased expressions of angiogenic genes (VEGF, VEGF-R1, ANGPT1, RTK) and increased mucosa layer (tunica mucosa) thickness but reduced muscle layer (Tunica muscularis) thickness. The SI is a target of prenatal nutritional programming, where late gestation overnutrition increased and shifted digestive capacity for carbohydrates toward the jejunum, whereas late gestation undernutrition predisposed for ileal angiogenesis and carbohydrate and fat hyperabsorptive capacity upon subsequent exposure to postnatal obesogenic diet., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Modulation of the human gut microbiota through probiotics, prebiotics and dietary fibre are recognised strategies to improve health and prevent disease. Yet we are only beginning to understand the impact of these interventions on the gut microbiota and the physiological consequences for the human host, thus forging the way towards evidence-based scientific validation. However, in many studies a percentage of participants can be defined as 'non-responders' and scientists are beginning to unravel what differentiates these from 'responders;' and it is now clear that an individual's baseline microbiota can influence an individual's response. Thus, microbiome composition can potentially serve as a biomarker to predict responsiveness to interventions, diets and dietary components enabling greater opportunities for its use towards disease prevention and health promotion. In Part I of this two-part review, we reviewed the current state of the science in terms of the gut microbiota and the role of diet and dietary components in shaping it and subsequent consequences for human health. In Part II, we examine the efficacy of gut-microbiota modulating therapies at different life stages and their potential to aid in the management of undernutrition and overnutrition. Given the significance of an individual's gut microbiota, we investigate the feasibility of microbiome testing and we discuss guidelines for evaluating the scientific validity of evidence for providing personalised microbiome-based dietary advice. Overall, this review highlights the potential value of the microbiome to prevent disease and maintain or promote health and in doing so, paves the pathway towards commercialisation., Competing Interests: The authors declare no conflict of interest.

Inflammation may be a mechanism of maternal programming because it has the capacity to alter the maternal environment and can persist postnatally in offspring tissues. This study evaluated the effects of restricted- and over-feeding on maternal and offspring inflammatory gene expression using reverse transcription (RT)-PCR arrays. Pregnant ewes were fed 60% (Restricted), 100% (Control), or 140% (Over) of National Research Council requirements beginning on day 30.2 ± 0.2 of gestation. Maternal (n = 8-9 ewes per diet) circulating nonesterified fatty acid (NEFA) and expression of 84 inflammatory genes were evaluated at five stages during gestation. Offspring (n = 6 per diet per age) inflammatory gene expression was evaluated in the circulation and liver at day 135 of gestation and birth. Throughout gestation, circulating NEFA increased in Restricted mothers but not Over. Expression of different proinflammatory mediators increased in Over and Restricted mothers, but was diet-dependent. Maternal diet altered offspring systemic and hepatic expression of genes involved in chemotaxis at late gestation and cytokine production at birth, but the offspring response was distinct from the maternal. In the perinatal offspring, maternal nutrient restriction increased hepatic chemokine (CC motif) ligand 16 and tumor necrosis factor expression. Alternately, maternal overnutrition increased offspring systemic expression of factors induced by hypoxia, whereas expression of factors regulating hepatocyte proliferation and differentiation were altered in the liver. Maternal nutrient restriction and overnutrition may differentially predispose offspring to liver dysfunction through an altered hepatic inflammatory microenvironment that contributes to immune and metabolic disturbances postnatally.

During episodes of undernutrition and overnutrition the mammalian preimplantation embryo undergoes molecular and metabolic adaptations to cope with nutrient deficits or excesses. Maternal adaptations also take place to keep a nutritional microenvironment favorable for oocyte development and embryo formation. This maternal-embryo communication takes place via several nutritional mediators. Although adaptive responses to malnutrition by both the mother and the embryo may ensure blastocyst formation, the resultant quality of the embryo can be compromised, leading to early pregnancy failure. Still, studies have shown that, although early embryonic mortality can be induced during malnutrition, the preimplantation embryo possesses an enormous plasticity that allows it to implant and achieve a full-term pregnancy under nutritional stress, even in extreme cases of malnutrition. This developmental strategy, however, may come with a price, as shown by the adverse developmental programming induced by even subtle nutritional challenges exerted exclusively during folliculogenesis and the preimplantation period, resulting in offspring with a higher risk of developing deleterious phenotypes in adulthood. Overall, current evidence indicates that malnutrition during the periconceptional period can induce cellular and molecular alterations in preimplantation embryos with repercussions for fertility and postnatal health., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity., (© 2014 Society for Endocrinology.)

Body energy stores and metabolic cues influence the onset of puberty. However, the pubertal impact of early nutritional challenges has been only fragmentarily addressed. We evaluated here the consequences, in terms of pubertal timing and hormonal markers, of various nutritional manipulations during pre- or postnatal maturation in rats of both sexes. Males and females were submitted to gestational undernutrition (UNG) or peripubertal (SUB) subnutrition or were raised in large (LL; underfeeding) or small (SL; overfeeding) litters. In addition, groups of UNG, LL, and SL rats were fed on a high-fat diet (HFD) after weaning. Postnatal overfeeding resulted in higher body weights (BWs) during pubertal transition in both sexes, but only SL males displayed overtly advanced external signs of puberty. Postnatal underfeeding persistently decreased BW gain during puberty, yet the magnitude of pubertal delay was greater in LL males. In contrast, regardless of postnatal nutrition, HFD tended to advance the onset of puberty in females but did not alter pubertal timing in males. Likewise, SUB females displayed a marked delay in BW gain and puberty onset, whereas despite similar reduction in BW, SUB males showed normal timing of puberty. These sex divergences were also detected in various hormonal and metabolic indices so that postnatal overnutrition consistently increased LH, FSH, leptin, and insulin levels only in pubertal females, whereas HFD decreased gonadotropin levels in SL females but increased them in SL males. Notably, UNG rats did not show signs of delayed puberty but displayed a striking sex dimorphism in serum insulin/glucose levels, regardless of the diet, so that only UNG males had signs of presumable insulin resistance. Our data disclose important sex differences in the impact of various early nutritional challenges on the timing of puberty, which may help to explain the different trends of altered puberty and related comorbidities between sexes.

Over the past 100 years, advances in pharmaceutical and medical technology have reduced the burden of communicable disease, and our appreciation of the mechanisms underlying the development of noncommunicable disease has broadened. During this time, a number of studies, both in humans and animal models, have highlighted the importance of maintaining an optimal diet during pregnancy. In particular, a number of studies support the hypothesis that suboptimal maternal protein and fat intake during pregnancy can have long-term effects on the growing fetus, and increase the likelihood of these offspring developing cardiovascular, renal, or metabolic diseases in adulthood. More recently, it has been shown that dietary intake of a number of micronutrients may offset or reverse the deleterious effects of macronutrient imbalance. Furthermore, maternal fat intake has also been identified as a major contributor to a healthy fetal environment, with a beneficial role for unsaturated fats during development as well as a beneficial impact on cell membrane physiology. Together these studies indicate that attempts to optimise maternal nutrition may prove to be an efficient and cost-effective strategy for preventing the development of cardiovascular, renal, or metabolic diseases.

Aims: To determine the characteristics of patients with diabetes who reported food insecurity at three diabetes clinics in western Kenya., Methods: This study includes routinely collected demographic data at the first presentation of patients with diabetes at clinics in western Kenya from 1 January 2006 to 24 September 2011. A validated questionnaire was used to assess food insecurity with descriptive and comparative statistics being used to analyse the food-secure and food-insecure populations., Results: The number of patients presenting to these clinics who were food-secure and those who were food-insecure was 1179 (68.0%) and 554 (32.0%), respectively. Comparative analysis shows a statistically significant difference in weight, BMI, the presence of a caretaker, and use of insulin between the two groups. These variables were lower in the food-insecure group. The overall assessment of the clinic population revealed an abnormally high mean HbA1c concentration of 81 mmol/mol (9.6%)., Conclusions: Despite the widely recognized contribution of caloric over-nutrition to the development of diabetes, this study highlights the high prevalence of food insecurity amongst patients with diabetes in rural, resource-constrained settings. Other factors, such as the lower prevalence of obesity, poor glucose control, challenges in the use of insulin because of the risk of hypoglycaemia, and varying subtypes of diabetes in this population, point to the need for additional research in understanding the aetiology, pathophysiology and optimum management of this condition, as well as understanding the effects of enhancing food security., (© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.)

Mounting evidence led us to hypothesize that i) function of the thyroid hormone (TH) axis can be programed by late gestation undernutrition (LG-UN) and ii) early-postnatal-life overnutrition (EL-ON) exacerbates the fetal impacts on TH axis function. In a 2 × 2 factorial experiment, 21 twin-bearing sheep were fed one of two diets during late gestation: NORM (fulfilling energy and protein requirements) or LOW (50% of NORM). From day 3 to 6 months after birth (around puberty), the twin lambs were assigned to each their diet: conventional (CONV) or high-carbohydrate, high-fat, where after half the lambs were killed. Remaining sheep (exclusively females) were fed the same moderate diet until 2 years of age (young adults). At 6 months and 2 years of age, fasting challenges were conducted and target tissues were collected at autopsy. LG-UN caused adult hyperthyroidism associated with increased thyroid expression of genes regulating TH synthesis and deiodination. In one or more of the target tissues, liver, cardiac muscle, and longissimus dorsi muscle, gene expressions were increased by LG-UN for TH receptors (THRA and THRB) and deiodinases but were decreased in visceral and subcutaneous adipose tissues. EL-ON increased TH levels in adolescent lambs, but this was reversed after diet correction and not evident in adulthood. We conclude that LG-UN programed TH axis function at the secretory level and differentially in target tissues, which was increasingly manifested with age. Differential TH signaling in adipose vs other tissues may be part of a mechanism whereby fetal malnutrition can predispose for obesity and other metabolic disorders.

To determine effects of maternal diet on in vitro fertilization (IVF) and early embryonic development, ewes (n = 48) were divided into control, overfed (ad libitum feeding), and underfed (60% of control) nutritional planes for 8 wk before oocyte collection. Follicular development was induced by twice-daily injections of FSH on days 13 and 14 of the estrous cycle, and ovaries and blood samples were collected on day 15 of the estrous cycle. During the 8-wk experiment, for control ewes BW and BCS did not change, but for overfed ewes mean (± SEM) BW and BCS increased (11.8 ± 1.1 kg and 2.0 ± 0.1, respectively) and for underfed ewes decreased (14.2 ± 0.9 kg and 0.7 ± 0.1, respectively). The number of follicles was determined; oocytes were collected and subjected to in vitro maturation and fertilization. After IVF, developing embryos were evaluated throughout the 8-d culture period. The proportion of cleaved oocytes after IVF and developing morula and blastocyst were less (P < 0.0001) in overfed and underfed ewes than in control ewes. However, number of visible follicles, total number of oocytes, number of healthy oocytes, and percentage of healthy oocytes were similar for control, overfed, and underfed ewes. Serum insulin concentration was greater (P < 0.05) in overfed ewes than in underfed ewes, estradiol 17-β (E(2)) concentration was greater (P < 0.05) in underfed ewes than in overfed ewes, but triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were similar in all treatment groups. These data show that inadequate feeding has a negative effect on oocyte quality which results in lower oocyte cleavage after IVF and morula and blastocyst formation; overfeeding increased serum insulin and underfeeding increased serum E(2) but not T(3) or T(4). These data emphasize the importance of diet for reproductive and metabolic functions. Furthermore, the mechanisms through which enhanced or decreased energy in diet affect oocyte quality and serum insulin and E(2) concentrations remain to be elucidated., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Both high and low maternal dietary intakes adversely affect fetal nutrient supply in adolescent sheep pregnancies. Aims were: (a) to assess the impact of prenatal nutrition on pregnancy outcome, offspring growth and offspring glucose metabolism and (b) to determine whether the offspring metabolic phenotype could then be altered by modifying postnatal nutrition. Dams carrying a single fetus were offered either an optimal control (C) intake to maintain adiposity throughout pregnancy, undernourished to maintain weight at conception but deplete maternal reserves (UN), or overnourished to promote rapid maternal growth and adiposity (ON). Placental weight and gestation length were reduced in ON dams and lamb birth weights were C>UN>ON (P < 0·001). All offspring were fed ad libitum from weaning to 6 months of age. ON offspring exhibited rapid catch-up growth and had increased fasting glucose and relative glucose intolerance compared with C offspring (P < 0·05). Irrespective of prenatal diet and sex, birth weight correlated negatively with these indices of glucose metabolism. From 7 to 12 months offspring either had continued ad libitum diet (ADLIB; to induce an obesogenic state) or a decreased ration appropriate for normal growth (NORM). At 12 months, the negative relationship between birth weight and indices of glucose metabolism persisted in ADLIB females (for example, fasting glucose, r - 0·632; P < 0·03) but was absent in NORM females and in both male groups. Therefore, low-birth-weight offspring from differentially achieved prenatal malnutrition exhibit an early adverse metabolic phenotype, and this can apparently be ameliorated by postnatal nutrition in females but not in males.

Perinatal undernutrition is known to disturb reproductive development, in particular by delaying the onset of puberty in certain species. Using a rat model, we studied whether hypernutrition after birth can rescue the delayed onset of puberty in intrauterine undernourished female rats. Pregnant rats were divided into two groups: the maternal normal nutrition (mNN, n = 8) and maternal undernutrition (mUN, n = 9) groups. In the mUN group, dams received 50% of the daily food intake of the mNN group from day 15 of pregnancy until delivery. Pups from both the mNN and mUN dams were then separated into two groups, based on their postnatal feeding conditions: control-normal nutrition (control-NN), control-hypernutrition (control-HN), Intrauterine growth retardation (IUGR)-normal nutrition (IUGR-NN), and IUGR-hypernutrition (IUGR-HN). Litter sizes of the hypernutrition groups were controlled to five pups per dam, and normal nutrition groups to 12-13 pups per dam. From postnatal day 30, pups were inspected daily for vaginal opening (VO). The age of VO in the IUGR-NN group was 35.7 ± 2.4 days (mean ± SD), which was significantly delayed compared to that of the control-NN group (33.8 ± 0.8 days). The age of VO in the IUGR-HN group was 35.5 ± 2.3 days, which was significantly delayed compared to that of the control-HN group (33.5 ± 0.8 days). Interestingly, the age of VO did not differ between the IUGR-NN and IUGR-HN groups. In conclusion, maternal undernutrition delays puberty in female offspring, and this delay in puberty cannot be rescued with hypernutrition after birth.

The goal of this review is to shed light on the role of maternal malnutrition in inducing epigenetic changes in gene expression, leading to alterations in fetal growth and development, and to altered postnatal phenotype and the development of metabolic disease. We present evidence supporting the concept that both maternal undernutrition and overnutrition can induce the same cadre of fetal organ and tissue abnormalities and lead to the same postnatal metabolic changes in the resulting offspring. Furthermore, we present evidence that in both overnourished and undernourished ovine pregnancies, fetuses experience a period of nutrient restriction as a result of alterations in placental delivery of maternal nutrients into the fetal compartment. We argue that this bout of reduced fetal nutrition in undernourished and overnourished pregnancies leads to the development of a thrifty phenotype in which the fetus attempts to alter the function of its tissues and organs to maximise its chances of survival in a postnatal environment that is deficient in nutrients. Importantly, we present evidence to support the concept that these phenotypic changes in offspring quality resulting from maternal malnutrition are transmitted to subsequent generations, independent of their maternal nutritional inputs.

To investigate the relationship between early nutritional experience, ontogeny of the small intestinal functions and predisposition to obesity development, the following experimental models of male Sprague-Dawley rats were used: 1) rats in which the quantity of nutrition was manipulated from birth to weaning (day 30) by adjusting the number of pups in the nest to 4 (SL), 10 (NL) and 16 pups (LL) and 2) littermates of SL, NL and LL rats fed either a standard or a hypercaloric diet from days 80 to 135 of age. The overfed SL pups were overweight after day 15 and became permanently obese, whereas the underfed smaller LL pups, due to accelerated growth and enhanced food intake from day 30 to day 35, attained a body fat level that did not differ from normally fed NL rats. Moreover, a significantly increased duodenal and jejunal alkaline phosphatase (AP) activity was found in SL and LL rats and these acquired somatic and intestinal characteristics persisted from weaning throughout life. Eight weeks of high-energy diet feeding elicited a similar pattern of intestinal response in SL and LL rats that was clearly different from NL rats. Despite energy over-consumption in these three groups, both SL and LL rats still displayed enhanced AP activity and showed a significant increase in protein/DNA ratio accompanied with a significant body fat accretion. These results indicate that the postnatally acquired small intestinal changes induced by over- and undernutrition could be involved in the similar predisposition to obesity risk in later life when caloric density of the diet is raised.

Malnutrition is a major problem in developing countries, and obesity and eating disorders are increasingly common in developing as well as developed countries. The reproductive axis is closely linked to nutritional status, especially undernutrition in the female, and inhibitory pathways involving detectors in the hind brain suppress ovulation in subjects with weight loss. Recovery may occur after minimal reacquisition of weight because energy balance is more important than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women of reproductive age causing amenorrhoea, infertility and, in those who do conceive, an increased likelihood of miscarriage. Obesity can affect reproduction through fat cell metabolism, steroids and secretion of proteins such as leptin and adiponectin and through changes induced at the level of important homeostatic factors such as pancreatic secretion of insulin, androgen synthesis by the ovary and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates that 9 to 25% of women in developed countries are severely obese, and obese mothers are much more likely to have obese children, especially if they have gestational diabetes. Obesity-associated anovulation may lead to infertility and to a higher risk of miscarriage. Management of anovulation with obesity involves diet and exercise as well as standard approaches to ovulation induction. Many obese women conceive without assistance, but pregnancies in obese women have increased rates of pregnancy-associated hypertension, gestational diabetes, large babies, Cesarean section and perinatal mortality and morbidity. Among contraceptors, the fear of weight gain affects uptake and continuation of hormonal contraceptives, although existing trials indicate that any such effects are small. For all methods of hormonal contraception, weight above 70 kg is associated with increased failure rates.