Adiponectin Signaling Modulates Fat Taste Responsiveness in Mice.

Background/objectives: Adiponectin, the most abundant peptide hormone secreted by adipocytes, is a well-known homeostatic factor regulating lipid metabolism and insulin sensitivity. It has been shown that the adiponectin receptor agonist AdipoRon selectively enhances cellular responses to fatty acids in human taste cells, and adiponectin selectively increases taste behavioral responses to intralipid in mice. However, the molecular mechanism underlying the physiological effects of adiponectin on fat taste in mice remains unclear.

Dietary fat differentially modulates the response of bone marrow-derived macrophages to TLR4 and NOD2 agonists.

Consumption of diets high in fat has been linked to the development of obesity and related metabolic complications. Such associations originate from the enhanced, chronic, low-grade inflammation mediated by macrophages in response to translocated bacteria, bacterial products, or dietary constituents such as fatty acids (FAs). Nucleotide-binding Oligomerization Domain 2 (NOD2) senses muramyl dipeptide (MDP), a component of bacterial peptidoglycan.

Adiponectin Enhances Fatty Acid Signaling in Human Taste Cells by Increasing Surface Expression of CD36.

Adiponectin, a key metabolic hormone, is secreted into the circulation by fat cells where it enhances insulin sensitivity and stimulates glucose and fatty acid metabolism. Adiponectin receptors are highly expressed in the taste system; however, their effects and mechanisms of action in the modulation of gustatory function remain unclear. We utilized an immortalized human fungiform taste cell line (HuFF) to investigate the effect of AdipoRon, an adiponectin receptor agonist, on fatty acid-induced calcium responses.

The Effect of Omega-9 on Bone Viscoelasticity and Strength in an Ovariectomized Diet-Fed Murine Model.

Few studies have investigated the effect of a monosaturated diet high in ω-9 on osteoporosis. We hypothesized that omega-9 (ω-9) protects ovariectomized (OVX) mice from a decline in bone microarchitecture, tissue loss, and mechanical strength, thereby serving as a modifiable dietary intervention against osteoporotic deterioration. Female C57BL/6J mice were assigned to sham-ovariectomy, ovariectomy, or ovariectomy + estradiol treatment prior to switching their feed to a diet high in ω-9 for 12 weeks.

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model.

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9.

GPR84 Is Essential for the Taste of Medium Chain Saturated Fatty Acids.

The ability of mammalian taste cells to respond to fatty acids (FAs) has garnered significant attention of late and has been proposed to represent a sixth primary taste. With few exceptions, studies on FA taste have centered exclusively on polyunsaturated FAs, most notably on linoleic acid. In the current study, we have identified an additional FA receptor, GPR84, in the gustatory system that responds to the medium-chain saturated FAs (MCFAs) in male mice.

Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice.

Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor's (GHS-R; a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models.

Sex differences in fat taste responsiveness are modulated by estradiol.

Sex as a biological variable has been the focus of increasing interest. Relatively few studies have focused, however, on differences in peripheral taste function between males and females. Nonetheless, there are reports of sex-dependent differences in chemosensitivity in the gustatory system.

Do polyunsaturated fatty acids protect against bone loss in our aging and osteoporotic population?

Age-related bone loss is inevitable in both men and women and there will soon be more people of extreme old age than ever before. Osteoporosis is a common chronic disease and as the proportion of older people, rate of obesity and the length of life increases, a rise in age-related degenerating bone diseases, disability, and prolonged dependency is projected. Fragility fractures are one of the most severe complications associated with both primary and secondary osteoporosis and current treatment strategies target weight-bearing exercise and pharmacological intervention, both with limited long-term success.

Spatiotemporal dynamic monitoring of fatty acid-receptor interaction on single living cells by multiplexed Raman imaging.

Numerous fatty acid receptors have proven to play critical roles in normal physiology. Interactions among these receptor types and their subsequent membrane trafficking has not been fully elucidated, due in part to the lack of efficient tools to track these cellular events. In this study, we fabricated the surface-enhanced Raman scattering (SERS)-based molecular sensors for detection of two putative fatty acid receptors, G protein-coupled receptor 120 (GPR120) and cluster of differentiation 36 (CD36), in a spatiotemporal manner in single cells.

Use of Surface-Enhanced Raman Scattering (SERS) Probes to Detect Fatty Acid Receptor Activity in a Microfluidic Device.

In this study, 4-mercaptobenzoic acid (MBA)-Au nanorods conjugated with a GPR120 antibody were developed as a highly sensitive surface-enhanced Raman spectroscopy (SERS) probe, and were applied to detect the interaction of fatty acids (FA) and their cognate receptor, GPR120, on the surface of human embryonic kidney cells (HEK293-GPRR120) cultured in a polydimethylsiloxane (PDMS) microfluidic device. Importantly, the two dominant characteristic SERS peaks of the Raman reporter molecule MBA, 1078 cm and 1581 cm, do not overlap with the main Raman peaks from the PDMS substrate when the appropriate spectral scanning range is selected, which effectively avoided the interference from the PDMS background signals. The proposed microfluidic device consisted of two parts, that is, the concentration gradient generator (CGG) and the cell culture well array.

SERS-fluorescence bimodal nanoprobes for in vitro imaging of fatty acid responsive receptor GPR120.

G-protein-coupled receptor 120 (GPR120), as a member of the rhodopsin family of G-protein-coupled receptors, has been shown to function as a sensor for dietary fat in the gustatory and digestive systems. Its specific role in the chemoreception of fatty acids, which is thought to be crucial in understanding the mechanism surrounding the control of fat intake and, accordingly, in the treatment of obesity, remains unclear. Here we report a novel surface-enhanced Raman spectroscopy (SERS)-fluorescence bimodal microscopic technique for detection and imaging of GPR120 in single living cells.

High-Fat Diet Alters the Orosensory Sensitivity to Fatty Acids in Obesity-Resistant but not Obesity-Prone Rats.

Gene-environment interactions play a role in the development of obesity but specific effects of diet on the orosensory detection of fatty acids have yet to be clarified. The objective of this study is to characterize the effect of prolonged (5-week) exposure to a high-fat (60%) diet on the behavioral sensitivity to the fatty acid linoleate following a conditioned taste aversion in obesity-prone and obesity-resistant rats. Exposure to the high-fat diet significantly enhanced the sensitivity of obesity-resistant (S5B/Pl) rats to linoleate while producing no effect on the fatty acid sensitivity for obesity-prone rats.

Cell signaling mechanisms of oro-gustatory detection of dietary fat: advances and challenges.

CD36 and two G-protein coupled receptors (GPCR), i.e., GPR120 and GPR40, have been implicated in the gustatory perception of dietary fats in rodents.

Sensing biophysical alterations of human lung epithelial cells (A549) in the context of toxicity effects of diesel exhaust particles.

Diesel exhaust particles (DEP) in urban air are associated with numerous respiratory diseases. The role of underlying biomechanics in cytotoxicity of individual lung cells relating to DEP exposure is unclear. In this study, atomic force microscopy (AFM), confocal Raman microspectroscopy (RM), and fluorescence (FL) microscopy were used to monitor alterations of single A549 cells exposed to DEP.

Investigation of free fatty acid associated recombinant membrane receptor protein expression in HEK293 cells using Raman spectroscopy, calcium imaging, and atomic force microscopy.

G-protein-coupled receptor 120 (GPR120) is a previously orphaned G-protein-coupled receptor that apparently functions as a sensor for dietary fat in the gustatory and digestive systems. In this study, a cDNA sequence encoding a doxycycline (Dox)-inducible mature peptide of GPR120 was inserted into an expression vector and transfected in HEK293 cells. We measured Raman spectra of single HEK293 cells as well as GPR120-expressing HEK293-GPR120 cells at a 48 h period following the additions of Dox at several concentrations.

Subcellular spectroscopic markers, topography and nanomechanics of human lung cancer and breast cancer cells examined by combined confocal Raman microspectroscopy and atomic force microscopy.

The nanostructures and hydrophobic properties of cancer cell membranes are important for membrane fusion and cell adhesion. They are directly related to cancer cell biophysical properties, including aggressive growth and migration. Additionally, chemical component analysis of the cancer cell membrane could potentially be applied in clinical diagnosis of cancer by identification of specific biomarker receptors expressed on cancer cell surfaces.

Biophysical assessment of single cell cytotoxicity: diesel exhaust particle-treated human aortic endothelial cells.

Exposure to diesel exhaust particles (DEPs), a major source of traffic-related air pollution, has become a serious health concern due to its adverse influences on human health including cardiovascular and respiratory disorders. To elucidate the relationship between biophysical properties (cell topography, cytoskeleton organizations, and cell mechanics) and functions of endothelial cells exposed to DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of DEPs on a model cell line from human aortic endothelial cells (HAECs). Fluorescence microscopy and flow cytometry were also applied to further explore DEP-induced cytotoxicity in HAECs.

Activation of oral trigeminal neurons by fatty acids is dependent upon intracellular calcium.

The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that conveys the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to stimulate rat trigeminal neurons has remained unexplored. Here, we found that several free fatty acids are capable of activating trigeminal neurons with different kinetics.

Targeted biodegradable nanoparticles for drug delivery to smooth muscle cells.

Targeted delivery of therapeutic agents to prevent smooth muscle cell (SMC) proliferation is important in averting restenosis (a narrowing of blood vessels). Since platelet derived growth factor (PDGF) receptors are over-expressed in proliferating SMCs after injury from cardiovascular interventions, such as angioplasty and stent implantation, our hypothesis is that conjugation of PDGF-BB (platelet-derived growth factor BB (homodimer)) peptides to biodegradable poly (D,L-lactic-co-glycolide) (PLGA) nanoparticles (NPs) would exhibit an increased uptake of these NPs by proliferating SMCs. In this study, poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles containing dexamethasone were formulated and conjugated with PDGF-BB peptides.

TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1.

Fatty acid-induced stimulation of enteroendocrine cells leads to release of the hormones such as cholecystokinin (CCK) that contribute to satiety. Recently, the fatty acid activated G protein-coupled receptor GPR120 has been shown to mediate long-chain unsaturated free fatty acid-induced CCK release from the enteroendocrine cell line, STC-1, yet the downstream signaling pathway remains unclear. Here we show that linoleic acid (LA) elicits membrane depolarization and an intracellular calcium rise in STC-1 cells and that these responses are significantly reduced when activity of G proteins or phospholipase C is blocked.

Effects of poly-(lactide-co-glycolide) nanoparticles on electrophysiological properties of enteroendocrine cells.

PLGA nanoparticles are widely used to deliver pharmacological compounds and genes to a variety of cell types. Despite the fact that many of these cells types depend critically on ion channel activity to function normally, there have been no studies on the effect of nanoparticles on the ion channel activity. To this end, we have investigated the effect of nanoparticles on cholecystokinin (CCK)-releasing enteroendocrine cell (EEC) line STC-1.

Transient receptor potential channel type M5 is essential for fat taste.

Until recently, dietary fat was considered to be tasteless, and its primary sensory attribute was believed to be its texture (Rolls et al., 1999; Verhagen et al., 2003).

Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells.

Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on (a) activation of sugar-gated cation channels and/or (b) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents.

Insulin activates epithelial sodium channel (ENaC) via phosphoinositide 3-kinase in mammalian taste receptor cells.

Diabetes is a profound disease that results in a severe lack of regulation of systemic salt and water balance. From our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel (ENaC), we have begun to investigate the ability of insulin to alter ENaC function with patch-clamp recording on isolated mouse taste receptor cells (TRCs). In fungiform and vallate TRCs that exhibit functional ENaC currents (e.