Changes in ghrelin isoforms after sleeve gastrectomy or gastric plication and their association with adiposity and metabolic profile.

Background & Aims: Sleeve gastrectomy (SG) and gastric plication (GP) are two widely performed bariatric techniques reducing the size of the stomach. The improvements observed following these procedures are not fully explained only by caloric restriction. Thus, we aimed at the analysis of adiposity and metabolism modifications in diet-induced obesity (DIO) rats submitted to SG or GP and correlate the changes with total ghrelin concentrations and its two different ghrelin isoforms.

FKBP51 inhibition ameliorates neurodegeneration and motor dysfunction in the neuromelanin-SNCA mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by the loss of neuromelanin (NM)-containing dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc) and the buildup of α-synuclein (α-syn) inclusions, called Lewy bodies. To investigate the roles of NM and α-syn in DA neuron degeneration, we modeled PD by inducing NM accumulation in a humanized α-syn mouse model (Snca; PAC-Tg(SNCA)) via the expression of human tyrosinase in the SN. We found that this mouse strain develops naturally progressive motor dysfunction and dopaminergic neuronal loss in the SN with aging.

IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy.

The contribution of interleukin-10 (IL-10), secreted by tumoral B cells, to the progression and shaping of the microenvironment in diffuse large B-cell lymphoma (DLBCL) with activated B-cell-like (ABC) phenotype is not yet completely understood. To shed light on this issue, we generated an immunocompetent mouse model of ABC-DLBCL with conditional knockout of IL-10 specifically in malignant B cells. Paradoxically, these mice had significantly worse overall survival when left untreated but experienced increased sensitivity to conventional anti-CD20 immunotherapy or regulatory T-cell depletion.

Differential mitochondrial adaptation and FNDC5 production in brown and white adipose tissue in response to cold and obesity.

Objective: Fibronectin type III domain-containing protein 5 (FNDC5) modulates adipocyte metabolism by increasing white and brown adipose tissue (WAT and BAT) browning and activity, respectively. We investigated whether FNDC5 can regulate visceral WAT and BAT adaptive thermogenesis by improving mitochondrial homeostasis in response to cold and obesity.

Methods: Adipose tissue expression of FNDC5 and factors involved in mitochondrial homeostasis were determined in patients with normal weight and obesity (n = 159) and in rats with diet-induced obesity after 1 week of cold exposure (n = 61).

Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD.

Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery.

Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis.

Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery.

Introduction: Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown.

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration.

Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of and its receptors in the colon from a rat model fed a normal diet.

Microspore embryogenesis induction by mannitol and TSA results in a complex regulation of epigenetic dynamics and gene expression in bread wheat.

Reprogramming of microspores development towards embryogenesis mediated by stress treatment constitutes the basis of doubled haploid production. Recently, compounds that alter histone post-translational modifications (PTMs) have been reported to enhance microspore embryogenesis (ME), by altering histones acetylation or methylation. However, epigenetic mechanisms underlying ME induction efficiency are poorly understood.

High plasma and lingual uroguanylin as potential contributors to changes in food preference after sleeve gastrectomy.

Background: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity.

The Differential Expression of the Inflammasomes in Adipose Tissue and Colon Influences the Development of Colon Cancer in a Context of Obesity by Regulating Intestinal Inflammation.

Background: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC.

Methods: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study.

Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats.

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats ( = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks.

Trichostatin A Affects Developmental Reprogramming of Bread Wheat Microspores towards an Embryogenic Route.

Microspores can be developmentally reprogrammed by the application of different stress treatments to initiate an embryogenic pathway leading to the production of doubled haploid (DH) plants. Epigenetic modifications are involved in cell reprogramming and totipotency in response to stress. To increase microspore embryogenesis (ME) efficiency in bread wheat, the effect of the histone deacetylase inhibitor trichostatin A (TSA) has been examined in two cultivars of wheat with different microspore embryogenesis response.

α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects.

α-Lipoic acid (α-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of α-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with α-Lip (100 and 250μM) for 24h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes.

Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN.

Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity.

From a histological and functional point of view, two types of adipose tissue can be identified. As opposed to the mainly unilocular white adipocytes, brown adipocytes possess plenty of small multilocular lipid droplets and dissipate energy as heat. Moreover, two distinct types of brown adipose cells exist.

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue.

There is increasing evidence that proteins associated with lipid droplets (LDs) play a key role in the coordination of lipid storage and mobilization in adipocytes. The small GTPase, RAB18, has been recently identified as a novel component of the protein coat of LDs and proposed to play a role in both β-adrenergic stimulation of lipolysis and insulin-induced lipogenesis in 3T3-L1 adipocytes. In order to better understand the role of Rab18 in the regulation of lipid metabolism in adipocytes, we evaluated the effects of age, fat location, metabolic status, and hormonal milieu on Rab18 expression in rodent white adipose tissue (WAT).

Short-term effects of sleeve gastrectomy and caloric restriction on blood pressure in diet-induced obese rats.

Background: Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity. The aim of the present study was to establish the effects of sleeve gastrectomy and caloric restriction on weight loss and cardiovascular parameters in diet-induced obese (DIO) rats.

Methods: Male Wistar DIO rats were subjected to surgical interventions (n = 30) (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals and compared to lean control rats) or dietary interventions (n = 40) (fed ad libitum a normal diet (ND) or a high-fat diet or an ND with a caloric restriction of 25 %).

Sleeve gastrectomy reduces blood pressure in obese (fa/fa) Zucker rats.

Background: Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity in humans and rodents with diet-induced obesity. The aim of the present study was to establish the effects of sleeve gastrectomy on weight loss and cardiovascular parameters in genetically obese (fa/fa) Zucker rats.

Methods: Eleven-week-old male obese (fa/fa) (n = 20) Zucker rats were assigned to three alternative procedures (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals) and compared with lean Zucker (Fa/Fa) rats (n = 9).

Biliopancreatic diversion induces villi elongation and cholecystokinin and ghrelin increase.

Introduction: Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. Our aim was to evaluate, in Sprague-Dawley rats, the histological and gut hormonal changes after Larrad-biliopancreatic diversion (Larrad-BPD).

Materials And Methods: Rats randomly underwent the following protocols: Larrad-BPD (n=4) versus pair fed (PF) (n=4).

Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade.

Objective: Glycerol constitutes an important metabolite for the control of lipid accumulation and glucose homeostasis. The impact of obesity and obesity-associated type 2 diabetes as well as the potential regulatory role of insulin and leptin on aquaglyceroporins (AQP) 3, 7, and 9 were analyzed.

Research Design And Methods: The tissue distribution and expression of AQP in biopsies of omental and sc adipose tissue as well as liver were analyzed in lean and obese Caucasian volunteers (n = 63).

Sleeve gastrectomy induces weight loss in diet-induced obese rats even if high-fat feeding is continued.

Background: Sleeve gastrectomy (SG) has been used for the surgical treatment of morbid obesity as a first or definitive procedure with satisfactory results. The objective of this study in rats was to establish the effects of SG on weight loss depending on the post-surgical type of diet followed.

Methods: Thirty male Wistar rats were fed ad libitum during 3 months on a high-fat diet (HFD) to induce obesity.

PRDM16: the interconvertible adipo-myocyte switch.

Both brown and white adipocytes were previously considered to be derived from the same precursor cell, despite being histologically and functionally different. However, a recent study shows that overexpression of the transcriptional regulator positive regulatory domain containing 16 (PRDM16) determines the development of brown adipocytes from a progenitor that expresses myoblast markers. Surprisingly, loss of PRDM16 from these precursors does not lead to white adipocyte differentiation.

Expression of leptin and adiponectin in the rat oviduct.

In mammals, the oviduct is an important source of factors that play key roles in reproductive and developmental events. The major components of oviduct fluid are oviduct-specific glycoproteins, but other proteins are synthesized and secreted by the oviduct epithelium. Leptin and adiponectin are two hormones originally identified in adipocytes that play a critical role not only in the control of energy balance and metabolism but also in diverse functions such as reproduction.

Inefficient chronic activation of parietal cells in Ae2a,b(-/-) mice.

In parietal cells, basolateral Ae2 Cl(-)/HCO(3)(-) exchanger (Slc4a2) appears to compensate for luminal H(+) pumping while providing Cl(-) for apical secretion. In mouse and rat, mRNA variants Ae2a, Ae2b1, Ae2b2, and Ae2c2 are all found in most tissues (although the latter at very low levels), whereas Ae2c1 is restricted to the stomach. We studied the acid secretory function of gastric mucosa in mice with targeted disruption of Ae2a, Ae2b1, and Ae2b2 (but not Ae2c) isoforms.