Air pollution accelerates the development of obesity and Alzheimer's disease: the role of leptin and inflammation - a mini-review.

Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD).

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.

Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release.

Multiple metabolic signals in the CeA regulate feeding: The role of AMPK.

Background: The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and controls energy balance. Recently, a cluster of neurons was identified as responsive to the orexigenic effect of ghrelin and fasting. However, the signaling pathway by which ghrelin and fasting induce feeding is unknown.

CLK2 in GABAergic neurons is critical in regulating energy balance and anxiety-like behavior in a gender-specific fashion.

Introduction: Cdc2-like kinase (CLK2) is a member of CLK kinases expressed in hypothalamic neurons and is activated in response to refeeding, leptin, or insulin. Diet-induced obesity and leptin receptor-deficient mice lack CLK2 signal in the hypothalamic neurons. The neurotransmiter gamma-aminobutyric acid (GABA) is among the most prevalent in the central nervous system (CNS), particularly in the hypothalamus.

Subchronic exposure to 1,2-naphthoquinone induces adipose tissue inflammation and changes the energy homeostasis of mice, partially due to TNFR1 and TLR4.

Air pollution affects energy homeostasis detrimentally. Yet, knowledge of how each isolated pollutant can impact energy metabolism remains incomplete. The present study was designed to investigate the distinct effects of 1,2-naphthoquinone (1,2-NQ) on energy metabolism since this pollutant increases at the same rate as diesel combustion.

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.

Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release.

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota.

Introduction: The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM) that impairs offspring's energy metabolism and gut microbiota composition.

Methods: Unexposed female and male C57BL/6J mice were mated.

Metformin acts in the gut and induces gut-liver crosstalk.

Metformin is the most prescribed drug for DM2, but its site and mechanism of action are still not well established. Here, we investigated the effects of metformin on basolateral intestinal glucose uptake (BIGU), and its consequences on hepatic glucose production (HGP). In diabetic patients and mice, the primary site of metformin action was the gut, increasing BIGU, evaluated through PET-CT.

Acute exercise reduces feeding by activating IL-6/Tubby axis in the mouse hypothalamus.

Acute exercise contributes to decreased feeding through leptin and interleukin/Janus kinase 2/signal transducers and activators of transcription 3 (IL-6/JAK2/STAT3) signaling. Considering the pleiotropic use of substrates by JAK2 and that JAK2 can phosphorylate the Tubby protein (TUB) in CHO-IR cells, we speculated that acute exercise can activate the IL-6/JAK2/TUB pathway to decrease food intake. We investigated whether acute exercise induced tyrosine phosphorylation and the association of TUB and JAK2 in the hypothalamus and if IL-6 is involved in this response, whether acute exercise increases the IL-6/TUB axis to regulate feeding, and if leptin has an additive effect over this mechanism.

Resistance exercise attenuates IKKε phosphorylation and hepatic fat accumulation of obese mice.

Obesity is associated with low-grade inflammation and disturbances in hepatic metabolism. This study aimed to investigate the effects of resistance exercise on inflammatory signalling related to IκB kinase (IKK) ɛ protein (IKKɛ) and on hepatic fat accumulation in obese mice. Male Swiss mice were distributed into three groups: control (CTL) fed with standard chow; obese (OB) mice induced by a high-fat diet (HFD); obese exercised (OB + RE) mice fed with HFD and submitted to a resistance exercise training.

Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPR in the hypothalamus of mice.

The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPR) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPR in hypothalamic cells are unclear.

Short-term exposure to air pollution (PM) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.

A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 μm (PM) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding.

Modulation of hypothalamic S6K1 and S6K2 alters feeding behavior and systemic glucose metabolism.

The mTOR/S6Ks signaling is one of the intracellular pathways important for metabolic control, acting both peripherally and centrally. In the hypothalamus, mTOR/S6Ks axis mediates the action of leptin and insulin and can modulate the expression of neuropeptides. We analyzed the role of different S6Ks isoforms in the hypothalamic regulation of metabolism.

Microbiota determines insulin sensitivity in TLR2-KO mice.

Introduction: Environmental factors have a key role in the control of gut microbiota and obesity. TLR2 knockout (TLR2) mice in some housing conditions are protected from diet-induced insulin resistance. However, in our housing conditions these animals are not protected from diet-induced insulin-resistance.

Growth hormone enhances the recovery of hypoglycemia ventromedial hypothalamic neurons.

Growth hormone (GH) is secreted during hypoglycemia, and GH-responsive neurons are found in brain areas containing glucose-sensing neurons that regulate the counter-regulatory response (CRR). However, whether GH modulates the CRR to hypoglycemia specific neuronal populations is currently unknown. Mice carrying ablation of GH receptor (GHR) either in leptin receptor (LepR)- or steroidogenic factor-1 (SF1)-expressing cells were studied.

Oral Glutamine Supplementation Reduces Obesity, Pro-Inflammatory Markers, and Improves Insulin Sensitivity in DIO Wistar Rats and Reduces Waist Circumference in Overweight and Obese Humans.

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated.

Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice.

Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion.

Effect of a diet containing folate and hazelnut oil capsule on the methylation level of the gene, lipid profile and oxidative stress in overweight or obese women.

Background: Studies of genes that play an important role in the development of obesity are needed, especially studies focusing on genes that regulate food intake and affect nutrient metabolism. For example, the beta-3 adrenergic receptor () responds to noradrenaline and mediates lipolysis in adipocytes.

Methods: This was a controlled intervention study involving 40 overweight and obese adult women in which food intake, anthropometric measurements, biochemical analyses, and methylation levels of the gene were evaluated before and after intervention.

Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L.

Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

Objective: Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent.

Results: Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow.

Blocking iNOS and endoplasmic reticulum stress synergistically improves insulin resistance in mice.

Objective: Recent data show that iNOS has an essential role in ER stress in obesity. However, whether iNOS is sufficient to account for obesity-induced ER stress and Unfolded Protein Response (UPR) has not yet been investigated. In the present study, we used iNOS knockout mice to investigate whether high-fat diet (HFD) can still induce residual ER stress-associated insulin resistance.