Plant miR8126-3p and miR8126-5p Decrease Lipid Accumulation through Modulation of Metabolic Genes in a Human Hepatocyte Model That Mimics Steatosis.

Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations are needed to determine the potential impact of plant miRNAs in NAFLD. This study aimed to identify plant miRNAs that could eventually modulate the expression of human metabolic genes and protect against the progression of hepatic steatosis.

Dietary fatty acid composition drives neuroinflammation and impaired behavior in obesity.

Nutrient composition in obesogenic diets may influence the severity of disorders associated with obesity such as insulin-resistance and chronic inflammation. Here we hypothesized that obesogenic diets rich in fat and varying in fatty acid composition, particularly in omega 6 (ω6) to omega 3 (ω3) ratio, have various effects on energy metabolism, neuroinflammation and behavior. Mice were fed either a control diet or a high fat diet (HFD) containing either low (LO), medium (ME) or high (HI) ω6/ω3 ratio.

[Thermoneutrality and animal study].

Animal models remain important for the study of human pathologies. The most widely used model (mouse) is an endothermic mammal like humans, maintained at ambient temperatures (22 °C). Its energy metabolism is overactivated, a situation rarely observed in humans thanks to various adaptations (clothing, heating…).

miR482f and miR482c-5p from edible plant-derived foods inhibit the expression of pro-inflammatory genes in human THP-1 macrophages.

Background: Edible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.

Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD metabolism in humans.

Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD), but limited knowledge of NAD metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD salvage pathway (nicotinamide and 1-methylnicotinamide) in humans.

The Association between Oxytocin and Lower Limb Osteoarthritis: A Prospective Cohort Study.

Oxytocin (OT), a neuropeptide best known for its role in emotional and social behaviors, has been linked to osteoarthritis (OA). This study aimed to investigate the serum OT level in hip and/or knee OA patients and to study its association with disease progression. Patients from the KHOALA cohort with symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) scores of 2 and 3) and follow-up at 5 years were included in this analysis.

Effects of Fatty Acid Metabolites on Adipocytes Britening: Role of Thromboxane A2.

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis.

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity.

In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting.

Delivery of miRNAs to the adipose organ for metabolic health.

Despite the increasing prevalence of obesity and diabetes, there is no efficient treatment to combat these epidemics. The adipose organ is the main site for energy storage and plays a pivotal role in whole body lipid metabolism and energy homeostasis, including remodeling and dysfunction of adipocytes and adipose tissues in obesity and diabetes. Thus, restoring and balancing metabolic functions in the adipose organ is in demand.

GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1.

Activation of thermogenic brown and beige adipocytes is considered as a strategy to improve metabolic control. Here, we identify GPR180 as a receptor regulating brown and beige adipocyte function and whole-body glucose homeostasis, whose expression in humans is associated with improved metabolic control. We demonstrate that GPR180 is not a GPCR but a component of the TGFβ signalling pathway and regulates the activity of the TGFβ receptor complex through SMAD3 phosphorylation.

microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis.

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology.

Gfi1 Loss Protects against Two Models of Induced Diabetes.

Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity and specification is still elusive. In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for specifically in the pancreas.

Relationship between Oxytocin and Osteoarthritis: Hope or Despair?

Oxytocin (OT) is involved in breastfeeding and childbirth and appears to play a role in regulating the bone matrix. OT is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and is released in response to numerous stimuli. It also appears to be produced by osteoblasts in the bone marrow, acting as a paracrine-autocrine regulator of bone formation.

Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes.

The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies. Using multi-well isothermal microcalorimetry, we have demonstrated that mature murine brown and brite adipocytes produce quantifiable heat upon β-AR stimulation, independently of any anaerobic mechanisms. Additionally, in brite adipocytes lacking UCP1 protein, β-AR stimulation still induces heat production, albeit to a much lower extent than in their wildtype counterparts, suggesting that UCP1 is an essential component of adrenergic induced thermogenesis in murine brite adipocytes exvivo.

Oxytocin and Bone: Review and Perspectives.

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture.

In vitro and ex vivo models of adipocytes.

Adipocytes are specialized cells with pleiotropic roles in physiology and pathology. Several types of fat cells with distinct metabolic properties coexist in various anatomically defined fat depots in mammals. White, beige, and brown adipocytes differ in their handling of lipids and thermogenic capacity, promoting differences in size and morphology.

No Effect of Dietary Fish Oil Supplementation on the Recruitment of Brown and Brite Adipocytes in Mice or Humans under Thermoneutral Conditions.

Scope: Brown and brite adipocytes within the mammalian adipose organ provide non-shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3-series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial.

The Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes.

Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity.

A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γ Binding Properties and Biological Activities.

A proprietary library of novel -aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound that possesses weak proadipogenic and peroxisome proliferator-activated receptor γ (PPARγ) activating properties. The systematic optimization of , in order to improve its PPARγ agonist activity, led to the synthesis of compound (-aryl-substituted valine derivative) that possesses dual PPARγ/PPARα agonistic activity. Structural and kinetic analyses reveal that occupies the typical ligand binding domain of the PPARγ agonists with, however, a unique high-affinity binding mode.

Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1.

Objective: Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes.

High prevalence for obesity in severe COVID-19: Possible links and perspectives towards patient stratification.

It is becoming obvious that in addition to aging and various hearth pathologies, excess of body weight, especially obesity is a major risk factor for severity of COVID-19 infection. Intriguingly the receptor for SARS-CoV-2 is ACE2, a member of the angiotensin receptor family that has a relatively large tissue distribution. This observation likely explains the multitude of symptoms that have been described from human patients.

Oxytocin Controls Chondrogenesis and Correlates with Osteoarthritis.

This study investigated the relationship of oxytocin (OT) to chondrogenesis and osteoarthritis (OA). Human bone marrow and multipotent adipose-derived stem cells were cultured in vitro in the absence or presence of OT and assayed for mRNA transcript expression along with histological and immunohistochemical analyses. To study the effects of OT in OA in vivo, a rat model and a human cohort of 63 men and 19 women with hand OA and healthy controls, respectively, were used.