Apple polyphenols induce browning of white adipose tissue

We and others have shown that apple polyphenols decrease adipose tissue mass. To better understand the underlying mechanisms and to expand clinical applicability, we herein examine whether apple polyphenols induce adipose thermogenic adaptations (browning) and prevent diet-induced obesity and related insulin resistance. In mice fed a standard diet, daily apple polyphenol consumption induced thermogenic adaptations in inguinal white adipose tissue (iWAT), based on increases in the expression of brown/beige adipocyte selective genes (Ucp1, Cidea, Tbx1, Cd137) and protein content of uncoupling protein 1 and mitochondrial oxidative phosphorylation enzymes. Among the upstream regulatory factors of browning, fibroblast growth factor 21 (FGF21) and peroxisome proliferator-activated receptor gamma coactivator 1 α (PGC-1α) levels were concomitantly up-regulated by apple polyphenols. In the primary cell culture experiment, the results did not support a direct action of apple polyphenols on beige adipogenesis. Instead, apple polyphenols increased tyrosine hydroxylase (a rate-limiting enzyme of catecholamine synthesis) in iWAT, which activates the adipocyte thermogenic program possibly via intratissue cellular communications. In high-fat fed mice, apple polyphenols induced beige adipocyte development in iWAT, reduced fat accumulation, and increased glucose disposal rates in the glucose and insulin tolerance tests. Taken together, dietary administration of apple polyphenols induced beige adipocyte development in iWAT possibly via activation/induction of the peripheral catecholamine synthesis–FGF21–PGC-1α cascade. Results from diet-induced obese mice indicate that apple polyphenols have therapeutic potential for obesity and related metabolic disorders.     

Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement

Background

Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.

Methods

This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis.

Results

Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale.

Conclusions

Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.     

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Background

Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.

Methods

In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3) or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA.

Results

During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A₂ (PLA₂) and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO), which binds PLA₂ and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR), which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes.

Conclusions

We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to increased cardiac hypertrophy, atherosclerosis, myocarditis/DCM and heart failure in male mice and humans.     

Pharmacological and nutritional agents promoting browning of white adipose tissue

The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli (“browning process”). Brown-like adipocytes that appear in white fat depots have been called “brite” (from brown-in-white) or “beige” adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.     

Mild-cold water swimming does not exacerbate white adipose tissue browning and brown adipose tissue activation in mice

Journal of Physiology and Biochemistry - The present study investigated the effects of swimming physical training either thermoneutral or below thermoneutral water temperature on white (WAT) and...     

Goshawk prey have more bacteria than non-prey

1. Predators often prey on individuals that are sick or otherwise weakened. Although previous studies have shown higher abundance of parasites in prey, whether prey have elevated loads of micro-organisms remains to be determined. 2. We quantified the abundance of bacteria and fungi on feathers of woodpigeons Columba palumbus L., jays Garrulus glandarius L. and blackbirds Turdus merula L. that either fell prey to goshawks Accipiter gentilis L. or were not depredated. 3. We found an almost three-fold increase in bacterial load of prey compared with non-prey, while there was no significant difference between prey and non-prey in level of fungal infection of the plumage. 4. The results were not confounded by differences in size or mass of feathers, date of collection of feathers, or date of analysis of feathers for micro-organisms. 5. These findings suggest a previously unknown contribution of bacteria to risk of predation, with important implications for behaviour, population ecology and community ecology.     

Cellular and molecular large‐scale features of fetal adipose tissue: Is bovine perirenal adipose tissue Brown1685

Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large-scale-molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post-conception (dpc) with the aim of identifying key cellular and molecular events in AT growth. The increase in AT weight from 110 to 260 dpc resulted from an increase in adipocyte volume and particularly adipocyte number that were concomitant with temporal changes in the abundance of 142 proteins revealed by proteomics. At 110 and 180 dpc, we identified proteins such as TCP1, FKBP4, or HSPD1 that may regulate adipocyte precursor proliferation by controlling cell-cycle progression and/or apoptosis or delaying PPARγ-induced differentiation. From 180 dpc, the up-regulation of PPARγ-induced proteins, lipogenic and lipolytic enzymes, and adipokine expression may underpin the differentiation and increase in adipocyte volume. Also from 180 dpc, we unexpectedly observed up-regulations in the β-subunit of ATP synthase, which is normally bypassed in brown AT, as well as in aldehyde dehydrogenases ALDH2 and ALDH9A1, which were predominantly expressed in mouse white AT. These results, together with the observed abundant unilocular adipocytes at 180 and 260 dpc, strongly suggest that fetal bovine perirenal AT has much more in common with white than with brown AT.     

Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process

Journal of Physiology and Biochemistry - The main function of brown adipose tissue (BAT) is thermogenesis, a process mediated by uncoupling protein 1 (UCP1), which is located in the inner...