An Eclectic Cast of Cellular Actors Orchestrates Innate Immune Responses in the Mechanisms Driving Obesity and Metabolic Perturbation.

The escalating problem of obesity and its multiple metabolic and cardiovascular complications threatens the health and longevity of humans throughout the world. The cause of obesity and one of its chief complications, insulin resistance, involves the participation of multiple distinct organs and cell types. From the brain to the periphery, cell-intrinsic and intercellular networks converge to stimulate and propagate increases in body mass and adiposity, as well as disturbances of insulin sensitivity. This review focuses on the roles of the cadre of innate immune cells, both those that are resident in metabolic organs and those that are recruited into these organs in response to cues elicited by stressors such as overnutrition and reduced physical activity. Beyond the typical cast of innate immune characters invoked in the mechanisms of metabolic perturbation in these settings, such as neutrophils and monocytes/macrophages, these actors are joined by bone marrow-derived cells, such as eosinophils and mast cells and the intriguing innate lymphoid cells, which are present in the circulation and in metabolic organ depots. Upon high-fat feeding or reduced physical activity, phenotypic modulation of the cast of plastic innate immune cells ensues, leading to the production of mediators that affect inflammation, lipid handling, and metabolic signaling. Furthermore, their consequent interactions with adaptive immune cells, including myriad T-cell and B-cell subsets, compound these complexities. Notably, many of these innate immune cell-elicited signals in overnutrition may be modulated by weight loss, such as that induced by bariatric surgery. Recently, exciting insights into the biology and pathobiology of these cell type-specific niches are being uncovered by state-of-the-art techniques such as single-cell RNA-sequencing. This review considers the evolution of this field of research on innate immunity in obesity and metabolic perturbation, as well as future directions.

Heat stress tolerance in relation to oxidative stress and antioxidants in Brassica juncea.

In the present study fifty genotypes of Brassica juncea were evaluated for heat stress tolerance in terms of biochemical components, in four day old seedlings. Heat shock was given at 45 degrees C for 4.5 hr and thereafter survival percentage, electrolyte leakage and chlorophyll content were estimated. Tolerant genotypes (10) registered survival greater than 65%, moderately tolerant (20) between 35-65% and susceptible (20) less than 35%. Electrolyte leakage was significantly (p < 0.001) higher in susceptible genotypes than in tolerant ones with respect to control seedlings. Chlorophyll content showed no significant variation among the tolerant, moderately tolerant and susceptible genotypes, although it registered a decline in response to heat stress. Lipid peroxidation, assessed by malondialdehyde (MDA) in stressed conditions was 4.66 (MDA g(-1) f. wt. of tissue) in tolerant genotypes, 7.44 (MDA g(-1) f. wt. of tissue) in susceptible genotypes and correlated significantly (r = 0.563) with electrolyte leakage. Increase in POD activity under heat stress was maximum in tolerant class with respect to control. CAT activity showed decrease after heat shock treatment in all the three classes but the decrease was 1.3 fold in tolerant genotypes as compared to 1.6 fold in susceptible genotypes. The non-enzymatic antioxidants glutathione and proline registered a significantly (< 0.01) high value in tolerant genotypes on heat shock treatment in comparison to susceptible genotypes corroborating the role of antioxidants in mitigating the effect of heat stress in Bjuncea. The antioxidants and proline seemed to play role in mitigating the effect of heat stress.

Optimizing microencapsulation of nisin with sodium alginate and guar gum.

Nisin is a widely used bacteriocin active against gram positive bacteria and is also reported to be active against some gram negative bacteria. Incorporation of nisin into food systems is another challenge as directly added nisin is prone to inactivation by food constituents. Encapsulation of nisin has been done so far in liposomes which is rather an expensive technology involving multiple processes. Other cost effective alternatives with good encapsulation efficiency and better control release properties are sought. Alginate is useful as a matrix for entrapment of bioactive compounds. Present study was aimed at optimizing conditions for microencapsulation of nisin using calcium alginate as primary wall material and guar gum as filler at different air pressures using response surface methodology. The optimum conditions were: sodium alginate concentration (2 % w/v), guar gum concentration (0.4 % w/v), and air pressure (0.5 bar gauge). The encapsulation efficiency of nisin in microcapsules produced under optimal conditions was 36.65 %.

Pharmacological antagonism of receptor for advanced glycation end products signaling promotes thermogenesis, healthful body mass and composition, and metabolism in mice.

OBJECTIVE: Optimal body mass and composition as well as metabolic fitness require tightly regulated and interconnected mechanisms across tissues. Disturbances in these regulatory networks tip the balance between metabolic health versus overweight and obesity and their complications. The authors previously demonstrated roles for the receptor for advanced glycation end products (RAGE) in obesity, as global- or adipocyte-specific deletion of Ager (the gene encoding RAGE) protected mice from high-fat diet-induced obesity and metabolic dysfunction. METHODS: To explore translational strategies evoked by these observations, a small molecule antagonist of RAGE signaling, RAGE229, was administered to lean mice and mice with obesity undergoing diet-induced weight loss. Body mass and composition and whole body and adipose tissue metabolism were examined. RESULTS: This study demonstrates that antagonism of RAGE signaling reduced body mass and adiposity and improved glucose, insulin, and lipid metabolism in lean male and female mice and in male mice with obesity undergoing weight loss. In adipose tissue and in human and mouse adipocytes, RAGE229 enhanced phosphorylation of protein kinase A substrates, which augmented lipolysis, mitochondrial function, and thermogenic programs. CONCLUSIONS: Pharmacological antagonism of RAGE signaling is a potent strategy to optimize healthful body mass and composition and metabolic fitness.

Effects of Intermittent Energy Restriction Alone and in Combination with Sprint Interval Training on Body Composition and Cardiometabolic Biomarkers in Individuals with Overweight and Obesity.

The popularity of intermittent fasting (IF) and high intensity (sprint) interval training (SIT) has increased in recent years amongst the general public due to their purported health benefits and feasibility of incorporation into daily life. The number of scientific studies investigating these strategies has also increased, however, very few have examined the combined effects, especially on body composition and cardiometabolic biomarkers, which is the primary aim of this investigation. A total of thirty-four male and female participants (age: 35.4 ± 8.4 y, body mass index (BMI): 31.3 ± 3.5 kg/m2, aerobic capacity (VO2peak) 27.7 ± 7.0 mL·kg−1·min−1) were randomized into one of three 16-week interventions: (1) 5:2 IF (2 non-consecutive days of fasting per week, 5 days on ad libitum eating), (2) supervised SIT (3 bouts per week of 20s cycling at 150% VO2peak followed by 40 s of active rest, total 10 min duration), and (3) a combination of both interventions. Body composition, haemodynamic and VO2peak were measured at 0, 8 and 16 weeks. Blood samples were also taken and analysed for lipid profiles and markers of glucose regulation. Both IF and IF/SIT significantly decreased body weight, fat mass and visceral fat compared to SIT only (p < 0.05), with no significant differences between diet and diet + exercise combined. The effects of diet and/or exercise on cardiometabolic biomarkers were mixed. Only exercise alone or with IF significantly increased cardiorespiratory fitness. The results suggest that energy restriction was the main driver of body composition enhancement, with little effect from the low volume SIT. Conversely, to achieve benefits in cardiorespiratory fitness, exercise is required.

The RAGE/DIAPH1 axis: mediator of obesity and proposed biomarker of human cardiometabolic disease.

Overweight and obesity are leading causes of cardiometabolic dysfunction. Despite extensive investigation, the mechanisms mediating the increase in these conditions are yet to be fully understood. Beyond endogenous formation of advanced glycation end products (AGEs) in overweight and obesity, exogenous sources of AGEs accrue through the heating, production and consumption of highly-processed foods. Evidence from cellular and mouse model systems indicates that the interaction of AGEs with their central cell surface receptor for AGE (RAGE) in adipocytes suppresses energy expenditure and that AGE/RAGE contributes to increased adipose inflammation and processes linked to insulin resistance. In human subjects, the circulating soluble forms of RAGE, which are mutable, may serve as biomarkers of obesity and weight loss. Antagonists of RAGE signaling, through blockade of the interaction of the RAGE cytoplasmic domain with the formin, Diaphanous-1 (DIAPH1), target aberrant RAGE activities in metabolic tissues. This review focuses on the potential roles for AGEs and other RAGE ligands and RAGE/DIAPH1 in the pathogenesis of overweight and obesity and their metabolic consequences.

Intermittent Fasting and High-Intensity Exercise Elicit Sexual-Dimorphic and Tissue-Specific Adaptations in Diet-Induced Obese Mice.

: The molecular adaptations that underpin body composition changes and health benefits of intermittent fasting (IF) and high-intensity interval training (HIIT) are unclear. The present study investigated these adaptations within the hypothalamus, white adipose and skeletal muscle tissue following 12 weeks of IF and/or HIIT in diet-induced obese mice. Mice (C57BL/6, 8-week-old, males/females) were fed high-fat (59%) and sugar (30%) water (HF/S) for 12 weeks followed by an additional 12 weeks of HF/S plus either IF, HIIT, combination (IF+HIIT) or HF/S only control (CON). Tissues were harvested at 12 and 24 weeks and analysed for various molecular markers. Hypothalamic NPY expression was significantly lower following IF+HIIT compared to CON in females. In adipose tissue, leptin expression was significantly lower following IF and IF+HIIT compared to CON in males and females. Males demonstrated increased markers of fat oxidation (HADH, FABP4) following IF+HIIT, whereas females demonstrated reduced markers of adipocyte differentiation/storage (CIDEC and FOXO1) following IF and/or IF+HIIT. In muscle, SIRT1, UCP3, PGC1α, and AS160 expression was significantly lower following IF compared to CON in males and/or females. This investigation suggests that males and females undertaking IF and HIIT may prevent weight gain via different mechanisms within the same tissue.

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females.

BACKGROUND: Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. METHODS: Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min- 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. RESULTS: FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. CONCLUSION: Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. TRIAL REGISTRATION: ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.

Intermittent Fasting with or without Exercise Prevents Weight Gain and Improves Lipids in Diet-Induced Obese Mice.

Intermittent fasting (IF) and high intensity interval training (HIIT) are effective lifestyle interventions for improving body composition and overall health. However, the long-term effects of IF and potential synergistic effects of combining IF with exercise are unclear. The purpose of the study was to investigate the long-term effects of IF, with or without HIIT, on body composition and markers of metabolic health in diet-induced obese mice. In a randosmised, controlled design, 8-week-old C57BL/6 mice (males (n = 39) and females (n = 49)) were fed a high fat (HF) and sugar (S) water diet (30% (w/v)) for 24-weeks but were separated into five groups at 12-weeks: (1) 'obese' baseline control (OBC); (2) no intervention (CON); (3) intermittent fasting (IF); (4) high intensity intermittent exercise (HIIT) and (5) combination of dietary and exercise intervention (IF + HIIT). Body composition, strength and blood variables were measured at 0, 10 and/or 12-weeks. Intermittent fasting with or without HIIT resulted in significantly less weight gain, fat mass accumulation and reduced serum low density lipoproteins (LDL) levels compared to HIIT and CON male mice (p < 0.05). The results suggest that IF, with or without HIIT, can be an effective strategy for weight gain prevention despite concurrently consuming a high fat and sugar diet.

High fat diet and associated changes in the expression of micro-RNAs in tissue: Lessons learned from animal studies.

Environment and genetic factors play an important role in the development of obesity, and diet is one of the main contributing factors to this disease. High fat intake is associated with body weight gain, leading to obesity and other metabolic diseases. MicroRNAs (miRNAs) are a group of small, noncoding RNAs that are important regulators of gene expression at posttranscriptional level. Studies have shown that high fat intake, independent of body weight status, can significantly impact both negatively and positively the expression of miRNAs and thus the biological function of tissues such as adipose, skeletal, and cardiac muscle, liver, neuronal, and endothelial. This review will summarize the effects of high calorie diet in the form of high fat intake on miRNA expression in various tissues of animal models and of high fat fed offspring. We will also briefly review the impact of different dietary lipids on miRNA expression. Given changes in miRNA expression have been associated with the development of many diseases including obesity, understanding their biological role could have important clinical implications and offer tangible therapeutic targets for the prevention, management, and/or treatment of obesity and other lifestyle-related disorders.