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1.
FASEB J ; 38(2): e23425, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38226852

ABSTRACT

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10-expressing adenovirus (Ad) vector (Ad-LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose-stimulated insulin secretion in Ad-LPLAT10-treated mice compared with that in control Ad vector-treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad-LPLAT10-treated mice. Serum from Ad-LPLAT10-treated mice showed increased glucose-stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver-specific LPLAT10 overexpression affect the pancreas and increase glucose-stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.


Subject(s)
1-Acylglycerophosphocholine O-Acyltransferase , Diabetes Mellitus, Type 2 , Glucose Intolerance , Animals , Mice , 1-Acylglycerophosphocholine O-Acyltransferase/genetics , Glucose/pharmacology , Insulin Secretion , Liver , Phosphatidylcholines , Phospholipids
2.
Angew Chem Int Ed Engl ; 59(22): 8464-8470, 2020 05 25.
Article in English | MEDLINE | ID: mdl-32129542

ABSTRACT

Shimalactones A and B are neuritogenic polyketides possessing characteristic oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene ring systems that are produced by the marine fungus Emericella variecolor GF10. We identified a candidate biosynthetic gene cluster and conducted heterologous expression analysis. Expression of ShmA polyketide synthase in Aspergillus oryzae resulted in the production of preshimalactone. Aspergillus oryzae and Saccharomyces cerevisiae transformants expressing ShmA and ShmB produced shimalactones A and B, thus suggesting that the double bicyclo-ring formation reactions proceed non-enzymatically from preshimalactone epoxide. DFT calculations strongly support the idea that oxabicyclo-ring formation and 8π-6π electrocyclization proceed spontaneously after opening of the preshimalactone epoxide ring through protonation. We confirmed the formation of preshimalactone epoxide in vitro, followed by its non-enzymatic conversion to shimalactones in the dark.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemistry , Lactones/chemistry , Lactones/metabolism , Aspergillus/genetics , Aspergillus/metabolism , Biotransformation , Cyclization , Multigene Family/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism
3.
Hum Brain Mapp ; 40(3): 804-817, 2019 02 15.
Article in English | MEDLINE | ID: mdl-30276935

ABSTRACT

An intention to move distorts the perception of time. For example, a visual stimulus presented during the preparation of manual movements is perceived longer than actual. Although neural mechanisms underlying this action-induced time distortion have been unclear, here we propose a new model in which the distortion is caused by a sensory-motor interaction mediated by alpha rhythm. It is generally known that viewing a stimulus induces a reduction in amplitude of occipital 10-Hz wave ("alpha-blocking"). Preparing manual movements are also known to reduce alpha power in the motor cortex ("mu-suppression"). When human participants prepared movements while viewing a stimulus, we found that those two types of classical alpha suppression interacted in the third (time-processing) region in the brain, inducing a prominent decrease in alpha power in the supplementary motor cortex (SMA). Interestingly, this alpha suppression in the SMA occurred in an asymmetric manner (such that troughs of alpha rhythm was more strongly suppressed than peaks), which can produce a gradual increase (slow shift of baseline) in neural activity. Since the neural processing in the SMA encodes a subjective time length for a sensory event, the increased activity in this region (by the asymmetric alpha suppression) would cause an overestimation of elapsed time, resulting in the action-induced time distortion. Those results showed a unique role of alpha wave enabling communications across distant (visual, motor, and time-processing) regions in the brain and further suggested a new type of sensory-motor interaction based on neural desynchronization (rather than synchronization).


Subject(s)
Brain/physiology , Time Perception/physiology , Adolescent , Adult , Alpha Rhythm/physiology , Female , Humans , Magnetoencephalography , Male , Middle Aged , Photic Stimulation , Visual Perception/physiology , Young Adult
4.
Brain Topogr ; 31(6): 1001-1013, 2018 11.
Article in English | MEDLINE | ID: mdl-29882034

ABSTRACT

Some researchers in aesthetics assume visual features related to aesthetic perception (e.g. golden ratio and symmetry) commonly embedded in masterpieces. If this is true, an intriguing hypothesis is that the human brain has neural circuitry specialized for the processing of visual beauty. We presently tested this hypothesis by combining a neuroimaging technique with the repetition suppression (RS) paradigm. Subjects (non-experts in art) viewed two images of sculptures sequentially presented. Some sculptures obeyed the golden ratio (canonical images), while the golden proportion were impaired in other sculptures (deformed images). We found that the occipito-temporal cortex in the right hemisphere showed the RS when a canonical sculpture (e.g. Venus de Milo) was repeatedly presented, but not when its deformed version was repeated. Furthermore, the right parietal cortex showed the RS to the canonical proportion even when two sculptures had different identities (e.g. Venus de Milo as the first stimulus and David di Michelangelo as the second), indicating that this region encodes the golden ratio as an abstract rule shared by different sculptures. Those results suggest two separate stages of neural processing for aesthetic information (one in the occipito-temporal and another in the parietal regions) that are hierarchically arranged in the human brain.


Subject(s)
Brain Mapping/psychology , Esthetics/psychology , Temporal Lobe/physiology , Adaptation, Physiological , Adult , Brain/physiology , Female , Humans , Male , Photic Stimulation , Young Adult
5.
Cognition ; 160: 51-61, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28049041

ABSTRACT

Although many studies have reported a distortion of subjective (internal) time during preparation and execution of actions, it is highly controversial whether actions cause a dilation or compression of time. In the present study, we tested a hypothesis that the previous controversy (dilation vs. compression) partly resulted from a mixture of two types of sensory inputs on which a time length was estimated; some studies asked subjects to measure the time of presentation for a single continuous stimulus (stimulus period, e.g. the duration of a long-lasting visual stimulus on a monitor) while others required estimation of a period without continuous stimulations (no-stimulus period, e.g. an inter-stimulus interval between two flashes). Results of our five experiments supported this hypothesis, showing that action preparation induced a dilation of a stimulus period, whereas a no-stimulus period was not subject to this dilation and sometimes can be compressed by action preparation. Those results provided a new insight into a previous view assuming a uniform dilation or compression of subjective time by actions. Our findings about the distinction between stimulus and no-stimulus periods also might contribute to a resolution of mixed results (action-induced dilation vs. compression) in a previous literature.


Subject(s)
Psychomotor Performance , Time Perception , Humans , Motor Activity , Psychometrics , Time Factors
6.
Sci Rep ; 6: 22049, 2016 Feb 26.
Article in English | MEDLINE | ID: mdl-26915796

ABSTRACT

When we encounter someone we dislike, we may momentarily display a reflexive disgust expression, only to follow-up with a forced smile and greeting. Our daily lives are replete with a mixture of true and fake expressions. Nevertheless, are these fake expressions really effective at hiding our true emotions? Here we show that brief emotional changes in the eyes (micro-expressions, thought to reflect true emotions) can be successfully concealed by follow-up mouth movements (e.g. a smile). In the same manner as backward masking, mouth movements of a face inhibited conscious detection of all types of micro-expressions in that face, even when viewers paid full attention to the eye region. This masking works only in a backward direction, however, because no disrupting effect was observed when the mouth change preceded the eye change. These results provide scientific evidence for everyday behaviours like smiling to dissemble, and further clarify a major reason for the difficulty we face in discriminating genuine from fake emotional expressions.


Subject(s)
Deception , Emotions , Eye Movements , Facial Expression , Mouth , Facial Recognition , Female , Humans , Male
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