Nutritional programming of brown adipose tissue

Maintenance of functional brown adipose tissue (BAT) beyond the newborn period, through its role in expending energy in thermogenesis, provides a potential target to prevent childhood obesity. As the body’s fat distribution can be programmed by nutrition in early life, this study investigated whether modifying the maternal diet in the immediate newborn period increases the thermogenic potential of major brown fat depots. In humans and sheep, UCP1 decreases after birth, thus, BAT gradually transitions to be white adipose tissue (WAT). Three major adipose tissue depots in sheep (sternal, perirenal and epicardial) were studied which are all populated with brown adipocytes in early postnatal life, and then undergo a transition to WAT by the end of first month of life. Heat production in BAT is mediated by uncoupling protein (UCP)1 and fatty acids have the potential to increase the amount of UCP1. The aim of this thesis was, therefore, to determine whether maternal fatty acid supplementation with a readily available short-chain fatty acid (i.e. canola or sunflower oil) modifies milk fatty acid profile and thus the development of adipose tissue in the offspring. Ewes, that each reared twin lambs, were fed a control diet or one supplemented with either 3% canola or sunflower oil from the day of delivery throughout lactation. Milk samples, ewe and lamb weights were taken at 7 and 28 days and offspring underwent tissue and blood sampling at either 7 or 28 days of age. The mRNA expression of regulatory genes associated with thermogenesis and fatty acid metabolism was measured. The abundance of UCP1 and other mitochondrial proteins was determined by immunohistochemistry and immunoblotting. Finally, microarray datasets were subjected to multi-region bioinformatics analysis in order to obtain biologically meaningful information about the examined adipose tissue depots. Supplementation of the maternal diet with canola oil, and to lesser extent, sunflower oil, resulted in decreased medium-chain saturated fatty acids and increased monounsaturated fatty acids content of milk. Omega-6 polyunsaturated fatty acids was also increased in milk of ewes that received the sunflower oil supplement. Although maternal fatty acid supplementation did not alter the mRNA expression of UCP1 in suckling lambs, tissue morphology (histology and microscopy) and protein abundance showed an increased UCP1 in adipose tissue located in the perirenal at 28 days of age compared with controls, suggesting canola oil delayed the rate of BAT loss. Microarray analysis indicate that each depot exhibited a distinct profile of gene expression and contained a small number of unique modules of co-expressed genes associated with distinct biological processes. Compared to other adipose tissue depots, perirenal showed a greater capability to respond to changes in the maternal diet. It was the most responsive adipose depot to maternal supplementation with canola oil causing an increase in the expression of some genes associated with the modulation of thermogenesis in BAT. With regards to genes involved in fatty acid metabolism, the epicardial depot appeared to be the primary site of unsaturated fatty acid synthesis in the first week of age, whilst this was dominant in the perirenal depot by day 28 of age when BAT is mostly converted into WAT. In conclusion, manipulating the fatty acid profile of milk ingested by the newborn may delay, or even prevent, UCP1 loss in early life. In addition, the recognition of the different characteristics of adipose tissue depots in early life expands the current understanding of adipose tissue development and the variations of their response to dietary intervention

Nutritional programming of brown adipose tissue

Maintenance of functional brown adipose tissue (BAT) beyond the newborn period, through its role in expending energy in thermogenesis, provides a potential target to prevent childhood obesity. As the body’s fat distribution can be programmed by nutrition in early life, this study investigated whether modifying the maternal diet in the immediate newborn period increases the thermogenic potential of major brown fat depots. In humans and sheep, UCP1 decreases after birth, thus, BAT gradually transitions to be white adipose tissue (WAT). Three major adipose tissue depots in sheep (sternal, perirenal and epicardial) were studied which are all populated with brown adipocytes in early postnatal life, and then undergo a transition to WAT by the end of first month of life. Heat production in BAT is mediated by uncoupling protein (UCP)1 and fatty acids have the potential to increase the amount of UCP1. The aim of this thesis was, therefore, to determine whether maternal fatty acid supplementation with a readily available short-chain fatty acid (i.e. canola or sunflower oil) modifies milk fatty acid profile and thus the development of adipose tissue in the offspring. Ewes, that each reared twin lambs, were fed a control diet or one supplemented with either 3% canola or sunflower oil from the day of delivery throughout lactation. Milk samples, ewe and lamb weights were taken at 7 and 28 days and offspring underwent tissue and blood sampling at either 7 or 28 days of age. The mRNA expression of regulatory genes associated with thermogenesis and fatty acid metabolism was measured. The abundance of UCP1 and other mitochondrial proteins was determined by immunohistochemistry and immunoblotting. Finally, microarray datasets were subjected to multi-region bioinformatics analysis in order to obtain biologically meaningful information about the examined adipose tissue depots. Supplementation of the maternal diet with canola oil, and to lesser extent, sunflower oil, resulted in decreased medium-chain saturated fatty acids and increased monounsaturated fatty acids content of milk. Omega-6 polyunsaturated fatty acids was also increased in milk of ewes that received the sunflower oil supplement. Although maternal fatty acid supplementation did not alter the mRNA expression of UCP1 in suckling lambs, tissue morphology (histology and microscopy) and protein abundance showed an increased UCP1 in adipose tissue located in the perirenal at 28 days of age compared with controls, suggesting canola oil delayed the rate of BAT loss. Microarray analysis indicate that each depot exhibited a distinct profile of gene expression and contained a small number of unique modules of co-expressed genes associated with distinct biological processes. Compared to other adipose tissue depots, perirenal showed a greater capability to respond to changes in the maternal diet. It was the most responsive adipose depot to maternal supplementation with canola oil causing an increase in the expression of some genes associated with the modulation of thermogenesis in BAT. With regards to genes involved in fatty acid metabolism, the epicardial depot appeared to be the primary site of unsaturated fatty acid synthesis in the first week of age, whilst this was dominant in the perirenal depot by day 28 of age when BAT is mostly converted into WAT. In conclusion, manipulating the fatty acid profile of milk ingested by the newborn may delay, or even prevent, UCP1 loss in early life. In addition, the recognition of the different characteristics of adipose tissue depots in early life expands the current understanding of adipose tissue development and the variations of their response to dietary intervention

Ontogeny and thermogenic role for sternal fat in female sheep

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat. In adult sheep, implanted temperature probes were used to characterise the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant within sternal than retroperitoneal fat and was only retained in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the post-prandial rise in temperature was greater and more prolonged in sternal than retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood when it shows a greater thermogenic response to feeding than muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals

Breakfast Skipping among a Multi-Ethnic Population of Young Men and Relationship with Sociodemographic Determinants and Weight Status

Breakfast skipping is linked with obesity incidence. This study was conducted to assess the prevalence of breakfast skipping among a multi-ethnic population of young men residing in Saudi Arabia and its relationship with sociodemographic determinants and weight status. A total of 3600 young men aged 20 to 35 years and living in Riyadh, Saudi Arabia, were involved in this cross-sectional study. Sociodemographic determinants and breakfast-consumption frequency were collected from subjects by personal interviews. This study defines breakfast skipping as skipping breakfast at least one day per week. Weight and height were measured following standardized methods. The prevalence of breakfast skipping was observed among 52.8% of the study subjects. Nationality was a predictor of breakfast skipping, with the lowest and highest rates of breakfast skipping reported among young men from Bangladesh (14.0%) and Saudi Arabia (86.5%), respectively. Weight status was another predictor of breakfast skipping, as the mean body mass index for breakfast skippers (25.4 kg/m2) was significantly (p-value < 0.001) higher than that for breakfast consumers (24.8 kg/m2). Overweight/obese subjects have a significantly higher rate of breakfast skipping (56.9%) than underweight/normal weight subjects (48.9%). In conclusion, breakfast skipping prevalence is relatively high among young men residing in Saudi Arabia. The findings confirm a relationship between breakfast skipping and sociodemographic determinants and weight status

Esculeoside A alleviates reproductive toxicity in streptozotocin-diabetic rats’ s model by activating Nrf2 signaling

This examination studied if Esculeoside A (ESA) alleviates reproductive toxicity in a type 1 diabetes mellitus (T1DM) rat model and if activating Nrf2 underlies this protection. T1DM was established by a single injection of STZ. Aged-matched adult control and STZ-DM rats were administered either the vehicle (5% carboxymethyl cellulose) or ESA (100 mg/kg). An additional group [STZ-DM + ESA (100 mg) + brusatol (2 m/kg] was added. All treatments were conducted for 16 weeks. ESA failed to attenuate weight loss, hyperglycemia, and hypoinsulinemia but significantly attenuated the associated dyslipidemia in STZ-DM rats. In parallel, ESA also enhanced total sperm count, motility, survival, reduced head and tail sperm abnormalities, increased circulatory concentrations of follicular stimulating hormone (FSH), testosterone, and Luteinizing hormone (LH), and stimulated the testicular expression of several steroidogenic enzymes (StAR, CYP11A1, CYP17A1, 3β-HSD1) in STZ-DM rats. These observations were associated with a higher testicular increase in the transcription, protein levels, and nuclear activities of Nrf2 that coincided with a reduction in the total levels of MDA and keap1 and a significant increase in the total levels of some antioxidants such as HO-1, SOD, and GSH. In concomitance, ESA reduced the testicular mRNA and nuclear concentrations of NF-κB and depressed the levels of TNF-α and IL-6. Brusatol prevented all these protective effects of ESA. In conclusion, activation of Nrf2 triggers the protective potential of ESA against reproductive toxicity in STZ-DM rats

The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK

This study examined the protective effect of 11-keto-β-boswellic acid (AKBA) against streptozotocin (STZ)-induced diabetic cardiomyopathy (DC) in rats and examined the possible mechanisms of action. Male rats were divided into 5 groups (n = 8/each): (1) control, AKBA (10 mg/kg, orally), STZ (65 mg/kg, i.p.), STZ + AKBA (10 mg/kg, orally), and STZ + AKBA + compound C (CC/an AMPK inhibitor, 0.2 mg/kg, i.p.). AKBA improved the structure and the systolic and diastolic functions of the left ventricles (LVs) of STZ rats. It also attenuated the increase in plasma glucose, plasma insulin, and serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), and free fatty acids (FFAs) in these diabetic rats. AKBA stimulated the ventricular activities of phosphofructokinase (PFK), pyruvate dehydrogenase (PDH), and acetyl CoA carboxylase (ACC); increased levels of malonyl CoA; and reduced levels of carnitine palmitoyltransferase I (CPT1), indicating improvement in glucose and FA oxidation. It also reduced levels of malondialdehyde (MDA); increased mitochondria efficiency and ATP production; stimulated mRNA, total, and nuclear levels of Nrf2; increased levels of glutathione (GSH), heme oxygenase (HO-1), superoxide dismutase (SOD), and catalase (CAT); but reduced the expression and nuclear translocation of NF-κB and levels of tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These effects were concomitant with increased activities of AMPK in the LVs of the control and STZ-diabetic rats. Treatment with CC abolished all these protective effects of AKBA. In conclusion, AKBA protects against DC in rats, mainly by activating the AMPK-dependent control of insulin release, cardiac metabolism, and antioxidant and anti-inflammatory effects

Prevalence of Fast Food Intake among a Multi-Ethnic Population of Young Men and Its Connection with Sociodemographic Determinants and Obesity

Fast food is commonly consumed by young adults. Eating fast food is connected with the risk of obesity and other related diseases. The present study examines the prevalence of fast food intake in a diverse sample of young men. This cross-sectional study included 3600 young men (20–35 years) who resided in Riyadh, KSA. The frequency of fast food intake was assessed using a valid and reliable questionnaire. Weekly and daily intake of fast food were the two outcome variables adopted to assess the intake frequency. Weight and height were measured. Fast food was eaten by 88.8% and 50.1% of participants weekly and daily, respectively. Fast food intake was predicted by the nationality of participants. The highest prevalence of weekly fast food intake (99.7%) was observed among Saudi, Egyptian, and Indian participants, while the lowest rate was observed among Sudanese participants (48.6%). The highest and lowest rates of daily intake were seen among Filipino (83.4%) and Bangladeshi (6.3%) participants. Obesity was another predictor of fast food intake. Obese participants had a significantly higher odds ratio of weekly (OR = 2.89, p = 0.006) and daily (OR = 1.39, p = 0.021) fast food intake than non-overweight/non-obese participants. In conclusion, fast food is frequently consumed by young men in KSA. Our findings link the likelihood of fast food intake to sociodemographic determinants and obesity

Differences in Overweight and Obesity Prevalence among Young Men from Twelve Middle Eastern and Asian Countries Living in Saudi Arabia

Objectives: This study was conducted to assess differences in the prevalence of overweight and obesity among young men from twelve Middle Eastern and Asian countries who live in Riyadh, Saudi Arabia. Methods: This study used a cross-sectional design and was conducted in Riyadh, Saudi Arabia. The body weight and height of 3600 young men (aged 20 to 35 years) were measured using standardized methods. The sociodemographic characteristics of the participants were collected using face-to-face interviews. Results: Overweight and obesity was reported in 48.3% of the study sample; 42.2% were overweight, and 6.2% were obese. The overweight and obesity rate was associated with the nationality of the participants. The lowest rate of overweight and obesity was observed among participants from Bangladesh (19.4%), while the highest rate was reported among participants from Egypt (67.5%). Older age and longer residency duration were associated with overweight and obesity risk among the subjects. Conclusion: The outcomes revealed a fairly high prevalence of overweight and obesity among participants. The notable disparity in overweight and obesity rates among participants of different nationalities is confirmed. The risk of overweight and obesity among young men in Saudi Arabia is associated with nationality, age, and residency duration

Differences in Overweight and Obesity Prevalence among Young Men from Twelve Middle Eastern and Asian Countries Living in Saudi Arabia

Objectives: This study was conducted to assess differences in the prevalence of overweight and obesity among young men from twelve Middle Eastern and Asian countries who live in Riyadh, Saudi Arabia. Methods: This study used a cross-sectional design and was conducted in Riyadh, Saudi Arabia. The body weight and height of 3600 young men (aged 20 to 35 years) were measured using standardized methods. The sociodemographic characteristics of the participants were collected using face-to-face interviews. Results: Overweight and obesity was reported in 48.3% of the study sample; 42.2% were overweight, and 6.2% were obese. The overweight and obesity rate was associated with the nationality of the participants. The lowest rate of overweight and obesity was observed among participants from Bangladesh (19.4%), while the highest rate was reported among participants from Egypt (67.5%). Older age and longer residency duration were associated with overweight and obesity risk among the subjects. Conclusion: The outcomes revealed a fairly high prevalence of overweight and obesity among participants. The notable disparity in overweight and obesity rates among participants of different nationalities is confirmed. The risk of overweight and obesity among young men in Saudi Arabia is associated with nationality, age, and residency duration