Search

Lipoprotein metabolism is essential for the growth and proliferation of cancer cells, and is involved in the supply of energy and cellular components. Lipoprotein lipase (LPL) is a very important enzyme in lipoprotein metabolism; however, the details underlying the mechanism of LPL secretion are unclear. Palbociclib is an antitumor drug that inhibits cell cycle progression and suppresses the growth of cancer cells. The effects of palbociclib on energy metabolism, particularly on lipid metabolism, have not been fully elucidated.We examined the regulation of LPL secretion, which is primarily involved in lipoprotein metabolism. FM3A mouse mammary tumor cells, which are hormone receptor-positive breast cancer cells, were treated with palbociclib, and the activity and protein levels of secreted LPL were measured. Moreover, the changes in intracellular lipid content were measured by fluorescence staining using Nile Red.FM3A cells were treated with palbociclib, the activity and protein content of secreted LPL were increased. The stimulatory secretion of LPL by palbociclib was suppressed by an intracellular CaOur data suggest that palbociclib causes intracellular lipid accumulation in breast cancer cells by stimulating Ca

The role of β-estradiol (E

The role of β-estradiol (E2) in lipoprotein metabolism in mammary tumors is unclear, therefore, we investigated the effect of E2 on the secretion of lipoprotein lipase (LPL) from mouse mammary tumor FM3A cells. E2-treated cells increased the secretion of active LPL from FM3A cells in a time- and dose-dependent manner. Activity of mitogen-activated protein kinase (MAPK) was increased in the tumor cells treated with E2, and enhanced secretion of LPL was suppressed by MAPK kinase 1/2 inhibitor, PD98059, extracellular signal-regulated kinase (ERK) 1/2 inhibitor, FR180204, p38 MAPK inhibitor, SB202190, and phosphatidyl inositol 3-kinase (PI3K) inhibitor, LY294002. In addition, the effect of E2 on LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but were not by a mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed secretion of LPL by E2. These results suggest that the stimulatory secretion of LPL by E2 from the tumor cells is closely associated with an activation of mTORC2 rather than mTORC1 possibly via the MAPK cascade.

Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country's aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.

Many heterotherms employ torpor to conserve energy to cope with food shortage. Food shortage affects not only energy budgets but also other aspects of nutritional status. In addition to serving as an energy substrate, dietary proteins also provide vital nutrients including essential amino acids, some of which cannot be synthesized de novo. We evaluated the hypothesis that dietary protein deficiency induces torpor as a means of adjusting protein metabolism in the African woodland dormouse (Graphiurus murinus), a rodent with a protein-rich diet and lacking a cecum, which limits the potential for hindgut fermentation and coprophagy. Dormice were fed control and non-protein diets with equivalent energy content every two weeks under thermoneutral conditions. While the dormice did not express torpor under control conditions, some did under protein-deficient conditions. Among dormice expressing torpor, one maintained energy intake comparable to that during the control diet period, whereas the other reduced energy intake due to spontaneously reduced food consumption. These results suggest that torpor can be induced directly or indirectly by dietary protein deficiency even in the absence of energy constraints and thermal stress. In either case, torpor in response to deficiency in certain nutrients can reduce demands of the nutrient.

This study aimed to evaluate life in disaster reconstruction public housing, and structurally clarify the relationship between the impression of the reconstruction from the viewpoint of the sufferers’ sense of recovery and the residents’ internal satisfaction. The target area of the study was the earthquake disaster reconstruction public housing in the Tago Nishi area, Sendai City, Miyagi Prefecture. The impression of the reconstruction, as expressed by people living in disaster recovery public housing, consists of an evaluation of external environments, such as the living environment and the working environment. Moreover, the impression of the reconstruction that is evaluated in the external environment is measured through a psychological evaluation, both before and after the restoration of the residence. Further, the impression of the reconstruction affects the satisfaction with life in the reconstruction public housing. This study quantitatively clarified this relationship as a model. The impression of the reconstruction was evaluated on the basis of three items – living environment, disaster threat, and work environment – which encompass the external environment of the residents. The results are as follows. The maintenance of the work environment was rendered an important factor to improve the impression of the reconstruction. As a result of measuring the differences between the seven psychological items before and after the earthquake, the prevalence of the feelings of “Anger/Joy,” “Depression/Bright,” and “Apathy/Willingness” made it clear that the monitoring of change in the area had a strong influence on the impression of the reconstruction. In addition, satisfaction with life, which makes up the residents’ internal environment, was evaluated using the following four items: Convenience, Comfort, Safety, and Community. The results made it evident that all four items had a strong influence on life satisfaction, and, among them comfort had the greatest influence.

Japanese Spanish mackerel Scomberomorus niphonius is a target species for stocking, but its biological characteristics at the juvenile stage are not well understood. Here, we investigated the high-temperature and starvation tolerances of hatchery-reared juveniles in captivity. We used juveniles of approximately 40 mm standard length, the size of juveniles released into the field. The upper incipient lethal temperature (50% lethal water temperature) was estimated to be 31.8 °C, higher than the maximum sea surface temperature in the field (approximately 29 °C). The critical thermal maximum was 34.8 °C, whereas it was 36.1 °C when juveniles were preliminarily acclimated to 31 °C for 24 h. Juveniles died from 3 to 11 days under nonfeeding conditions at 20 °C, but from 2 to 7 days at 27 °C. This information is expected to contribute to the development of the production of juvenile Japanese Spanish mackerel., This study was partly supported by JSPS KAKENHI Grant Number 19K06207.

Urban parks are open space with trees that provides a place of relaxation and peace for residence. Urban parks have been rapidly constructed in Korea since the Seoul Olympics (1988). On the other hand, In Japan the supply of urban parks is sufficient, and the maintenance and utilization of park that have been stocked during the period of high growth has become a problem. We thought it necessary to compare the parks of Korea and Japan during the period when the environment changed significantly after the Seoul Olympics. This purpose of study is to clarify the characteristics of Korea and Japan parks by comparing them. As a result of this study, the following features were clarified. In the transition of urban park politics, we found that there are similarities in responding to issues such as "diversifying needs", "park master plan", and "private entry". In both Korea and Japan, the important direction of future park policy is considered to be “use and maintenance”.

High schools in Gunma Prefecture, Japan, conducted an environmental engineering education program for international students from Southeast Asia for 13 years from 1998 to 2010. The purpose of this study is to understand the impact of the program on former international students and Japanese high schools as of now, 10 years after the end of the environmental engineering program. International students stayed in a Japanese home for a year and learned environmental engineering technology while interacting with Japanese high school students. In order to sort out the different types of exchange activities between former international students and Japanese high schools, and to do a post analysis, we conducted a survey of former international students and Japanese high school students, Southeast Asian and Japanese high school staff and host families.Using the survey data, a logic model for the environmental engineering education program was created. As a result, it was found that three elements of cross-cultural understanding, training agricultural engineers, and acquiring language skills are important for global human resource development. And it was found that the three elements involved four resources/inputs: homestay families, support for language learning, acquisition of agricultural technology, and learning and living experiences in foreign countries. It was found that the four resources exist all over the country, the program is likely to be applicable nationwide, and the global human resource development program can be disseminated anywhere.

The aim of the present study is to indicate objective position of a local city other than the prefectural capital location by formulating model of urban power and current condition evaluation. Specific methods are as follows: 1) formulate a model of urban power; 2) evaluate the current situation of Takasaki City; and 3) clarify direction to tackle in order to improve Takasaki City in the future by formulating model of urban power and current condition evaluation. The results obtained in the present study can be summarized as follows: 1) In order to maintain urban power of local cities, it is necessary to industrial activities that create bustling communities such as commerce; 2) It is indispensable to enhance transportation system such as Shinkansen, railway and expressway, and to enhance the bases of home center and department store; and 3) The annual sales of goods value of Takasaki City is larger than that of Maebashi City, the prefectural office location in Gunma, and is considered to be contributed by department store, Shinkansen, and expressway.

Living while feeling various green effects is considered an effective tool to adapt to the situation of declining population and the aging population or to live an environmentally friendly life. To realize this, it is necessary to have a green zone management policy through cooperation between the administration and residents. Particularly, open gardens (* OG) as one of the private greening areas are expected to have great effects on the viewpoint of town planning. In the task of OG, "trigger and form of activity", "increase participants" and "increase awareness" are soft issues in sustainability. We thought that these could greatly influence the citizen's future activities. Therefore, we focused on this research. Therefore, to solve the above three major problems, this research grasped "situation of efforts by administrators and OG organizers in the case of OG of Maebashi City” and “perception of neighborhood residents' OG activities". The purpose of this research was to obtain basic knowledge for improvement of "issues for the sustainability". As a conclusion, "Shikishima OG" was not a limited activity of merely a favorite group, but more than half of the residents were recognized in the area around Shikishima Park. In addition, 80% of those inhabitants regarded positively as "Shikishima OG contributes to local community development". Furthermore, we could grasp that "improvement of the landscape of the district" was the most expected by these inhabitants in terms of "community development".

Daily torpor is a strategy used by some overwintering small endotherms to aid in energy conservation. However, the pattern of torpor varies among individuals within species and populations, even under the same environmental conditions, with significant implications for survival rate and reproductive success. Body mass is one factor that may influence this variation, especially in some small mammals that accumulate fat stores prior to overwintering. However, to our knowledge there has been no previous study examining the detailed relationships between torpor expression and body mass change in small mammals that hoard food as an energy resource during winter. The large Japanese field mouse, Apodemus speciosus, whose winter survival strategy depends on food caches instead of fat stores, displays daily torpor under artificial winter conditions (short-day photoperiod and cold). The present study clarifies the characteristics and patterns of daily torpor and body mass change in this species in the laboratory. Although expression of daily torpor was facilitated progressively as in other species, the observed patterns of torpor expression and body mass change showed considerable individual variation. Moreover, there was no obvious correlation between body mass and daily torpor expression. Therefore, it is suggested that in A. speciosus body mass may not contribute to individual variation of daily torpor during winter. Daily torpor during winter may be adjusted by not only mechanisms common to other small mammals, but also species-specific factors relating to the external or internal reserves of energy in small mammals.

Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.

Both cholesterol and α-tocopherol are essential lipophilic nutrients for humans and animals. Although cholesterol in excess causes severe problems such as coronary heart disease, it is a necessary component of cell membranes and is the precursor for the biosynthesis of steroid hormones and bile acids. Niemann-Pick C1-like 1 (NPC1L1) is a cholesterol transporter that is highly expressed in the small intestine and liver in humans and plays an important role in cholesterol homeostasis. Cholesterol promotes NPC1L1 endocytosis, which is an early step in cholesterol uptake. Furthermore, α-tocopherol is the most active form of vitamin E, and sufficient amounts of vitamin E are critical for health. It has been reported that NPC1L1 mediates α-tocopherol absorption; however, the mechanisms underlying this process are unknown. In this study, we found that treatment of cells that stably express NPC1L1-GFP with α-tocopherol promotes NPC1L1 endocytosis, and the NPC1L1 inhibitor, ezetimibe, efficiently prevents the α-tocopherol-induced endocytosis of NPC1L1. Cholesterol binding to the N-terminal domain (NTD) of NPC1L1 (NPC1L1-NTD) is essential for NPC1L1-mediated cholesterol absorption. We found that α-tocopherol competitively binds NPC1L1-NTD with cholesterol. Furthermore, when cells stably expressed NPC1L1ΔNTD-GFP, α-tocopherol could not induce the endocytosis of NPC1L1ΔNTD. Taken together, these results demonstrate that NPC1L1 recognizes α-tocopherol via its NTD and mediates α-tocopherol uptake through the same mechanism as cholesterol absorption.

Polymorphisms in genes involved in lipid metabolism have been reported to be associated with fatty acid composition of adipose tissue. However, the relationship of these polymorphisms with premortem ultrasonic traits is unknown. The objective of this study, therefore, was to assess the association between polymorphisms in fatty acid synthase, stearoyl-coenzyme A desaturase (SCD), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol acyltransferase 1, and nuclear receptor subfamily 1, group H, number 3 genes with ultrasonic and carcass traits in Japanese Black steers (n = 300) under progeny testing at the Livestock Improvement Association of Miyazaki. To have a comprehensive analysis of the association between the aforementioned genetic polymorphisms and ultrasonic traits, longitudinal measurements of ultrasonic traits were taken. Furthermore, the association of these genetic polymorphisms and carcass traits was evaluated. The polymorphisms in the SCD gene and SREBP1 were associated (P

Background Prazosin is an α1 adrenoceptor antagonist used in pharmacotherapy for the treatment of hypertension. Prazosin alters lipid metabolism in vivo , but the involved mechanism is not fully understood. In this study, we investigated the mechanism underlying the alteration of lipid metabolism. We show that the prazosin-stimulated release of hepatic triacylglyceride lipase (HTGL) from primary cultured rat hepatocytes involved Ca 2+ /calmodulin-dependent protein kinase II (CaMK-II) activation. Methods Primary cultured rat hepatocytes were incubated with prazosin and other agents. The hepatocytes were used in the CaMK-II and protein kinase A (PKA) activity assay. The supernatant was used in the HTGL activity assay and western blotting. Results Prazosin-stimulated HTGL release was suppressed by the inositol triphosphate receptor inhibitor xestospongin C and by the calmodulin inhibitor trifluoperazine but not by the protein kinase C inhibitor chelerythrine chloride or a diacylglycerol kinase inhibitor (R59949). Furthermore, the calmodulin-dependent protein kinase II (CaMK-II) activity in prazosin-treated hepatocytes increased in a time- and dose-dependent manner. The cAMP-dependent PKA activity of prazosin-stimulated hepatocytes was suppressed by a phospholipase C (PLC) inhibitor (U-73122), trifluoperazine, and a CaMK-II inhibitor (KN-93). Conclusions These results suggested that prazosin-stimulated HTGL release from hepatocytes was caused by activation of PKA associated with stimulation of CaMK-II activity through a signal cascade from PLC.

The mammalian gastrointestinal tract has evolved to facilitate food utilisation. Hamsters within the subfamily Cricetinae (Rodentia, Cricetidae) have a compartmentalised stomach consisting of a forestomach and a glandular stomach. The role of the forestomach in hamsters has long been discussed. In this study, we evaluated the microflora and volatile fatty acid contents of the large forestomach and caecum of a greater long-tailed hamster (Tscherskia triton). The estimated bacterial biodiversity in the forestomach based on 16S rRNA library sequencing analyses was low (sequence n = 226, Shannon index H′ = 2.12) compared to that in the rumen of ruminants. In contrast, the bacterial diversity in the caecum was very high (n = 259, H′ = 4.45), and comparable to that of other hindgut fermenters. The forestomach bacterial flora was dominated by Lactobacillus spp. (179/226 clones), and high concentrations of lactic acid were observed in the forestomach. These results indicate that the forestomach does not function like the rumen of ruminants, but that lactic acid fermentation does take place in this compartment. The caecum is thought to play a more important role in food digestion via fermentation by symbiotic microbes than the forestomach. When all cloned 16S rRNA gene sequences (n = 485) were grouped into operational taxonomic units (OTUs) with 97% similarity, the majority of clones isolated from the forestomach contents were also present in the caecum (85.4%), although fewer clones isolated from the caecum contents shared OTUs with clones from the forestomach (19.3%). Based on these results, we hypothesise that bacteria were transferred from the caecum to the forestomach by coprophagy.

In mammals, social tolerance among females, the philopatric sex, is formed through continued physical proximity between kin after offspring are weaned. However, the benefits of continued close association may be outweighed by costs such as local resource competition and risk of inbreeding. We hypothesized that for ‘philopatric females’, a flexible tendency towards either natal dispersal or philopatry is an important behavioral response to changes in social conditions. We examined this using an asocial rodent, Apodemus speciosus, which exhibits two discrete breeding seasons, one in spring and the second in autumn. Daughters and mothers were shown to recognize each other as kin at the time of weaning in both seasons. In spring, some mothers reproduced twice, and some first-litter daughters matured and reproduced in the same season. In autumn, however, only mothers reproduced, and there were no second litters. In spring, the proportion of natal dispersers was higher among weaned offspring whose mother remained present than those whose mother was absent, while in autumn, natal dispersal was more frequent when the mother was absent than when she remained. Sons dispersed earlier than their female littermates. Population density alone is insufficient to explain these patterns. We suggest that variable levels of reproductive competition between female kin result in seasonal differences in female natal dispersal. Breeding condition can be modulated by environmental factors, and the promotion of reproductive activity of females in spring may cause natal dispersal of daughters, while the inhibition of reproductive activity in autumn may permit philopatry.

Many small mammal species use torpor as a strategy for reducing energy expenditure in winter. Some rodent hibernators also hoard food to provide reserves of energy, and individuals with large hoards express less torpor than those with smaller reserves. These facts imply that animals can recognize levels of food availability, but where food is very plentiful, it is unclear whether torpor expression is affected by temporal changes in the extent of food overabundance. Moreover, the relationship between daily torpor and excess food availability has not been clearly established. The large Japanese field mouse Apodemus speciosus caches food for use as a winter energy resource and exhibits daily torpor under artificial winter conditions. The present study examined whether individuals exposed to different magnitudes of overabundant food exhibited differences in expression of daily torpor, and secondly whether torpor expression varied in response to changes in the overall quantity of overabundant food. It was observed that while absolute quantities of overabundant food did not appear to affect daily torpor expression, the mice did respond to changes in food availability, even when food remained overabundant. This suggests that the mice respond to fluctuations in food availability, even where these changes do not place any constraint on energy budgets. Thus recognition of changing food availability cannot be a purely physiological response to shortage or plenty, and may contribute to predictions of future energy availability. The expression of torpor was inhibited in response to increasing food availability, and the mice used shallower torpor when food availability increased to superabundance. These findings suggest that daily torpor may be regulated not only physiologically in response to energy constraints but also psychologically, via recognition of food availability.

Daily torpor is a physiological adaptation in small mammals and birds, characterised by drastic reductions in metabolism and body temperature. Energy-constraining conditions, such as cold and starvation, are known to cause the expression of daily torpor. However, the reason for high degrees of inter- and intra- individual variation in torpor expression (TE) in similar situations is not clear. As littermates of altricial animals are exposed to an uneven allocation of maternal resources from conception to weaning, we tested whether early nutritional experiences have long-term effects on TE in adults. We used full-sibling littermates of laboratory mice that as adults were starved overnight to induce torpor. We measured body weight from birth until adulthood as an indicator of nutritional status, and calculated the relative body weight (RBW) as an indicator of the difference in nutritional status within a litter. After maturation, we subjected mice to five repeated torpor induction trials involving 24 hours of fasting and 5 days of recovery. Half of the female mice displayed great individual variation in TE, whereas male mice rarely exhibited daily torpor. In females, RBW at birth influenced TE, irrespective of body weight in adulthood; thus, female mice born with low RBWs displayed high TE in adulthood. In conclusion, we provide evidence that TE in mice differs among littermates, and that this variation is linked closely to heterogeneous nutritional experiences during the foetal period.

This study investigated the little known winter ecology of Japanese dormice by monitoring body temperature patterns and winter activity in captive and free-living animals. Before onset of hibernation, animals exhibited a transitional phase characterized by frequent bouts of daily torpor. During hibernation itself, dormice aroused periodically from torpor but never foraged during arousals. Torpor bout duration tended to be shorter around the beginning and end of the hibernation period than during the intervening mid-hibernation period. In a further radio-tracking study of two free-living dormice, both were observed to construct a shallow underground hibernaculum at a depth of 1–5 cm and to enter hibernation alone. One individual left the nest after it was disturbed, while the other dormouse stayed in its nest and continued hibernating normally, exhibiting periodic arousal but never feeding or moving from the hibernaculum. These first detailed observations of hibernation in Japanese dormice are in good accordance with previous studies of European dormouse species.

Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection. Comparison of amino acid sequences between the rat and mouse CAT1s shows amino acid insertions in the rat protein near the Eco-MLV-binding motif. In addition to the insertion present in the rat CAT1, the hamster CAT1 has additional amino acid insertions. In contrast, tunicamycin treatment of mink and human cells does not elevate the infection, because their CAT1s do not have the Eco-MLV-binding motif. To define the evolutionary pathway of the Eco-MLV receptor, we analyzed CAT1 sequences and susceptibility to Eco-MLV infection of other several murinae animals, including the southern vole (Microtus rossiaemeridionalis), large Japanese field mouse (Apodemus speciosus), and Eurasian harvest mouse ( Micromys minutus). Eco-MLV infection was enhanced by tunicamycin in these cells, and their CAT1 sequences have the insertions like the hamster CAT1. Phylogenetic analysis of mammalian CAT1s suggested that the ancestral CAT1 does not have the Eco-MLV-binding motif, like the human CAT1, and the mouse CAT1 is thought to be generated by the amino acid deletions in the third extracellular loop of CAT1., Virus Genes, 48(3), pp.448-456; 2014

We recently found that hepatic triglyceride lipase (HTGL) was released from primary cultured rat hepatocytes after treatment with prazosin, an antagonist of alpha-1 adrenoceptors. However, the details of prazosin-induced HTGL release remain uncertain. Here we investigated whether changes in cAMP levels in hepatocytes were related to HTGL release from prazosin-stimulated hepatocytes. When hepatocytes were treated with prazosin, cAMP levels during stimulated release of HTGL increased in a time- and dose-dependent manner. Stimulated release of HTGL was suppressed by the adenylate cyclase inhibitors MDL-12,330A and 2',5'-dideoxyadenosine. Further, cAMP-dependent protein kinase A (PKA) activity in prazosin-stimulated hepatocytes also increased in a time- and dose-dependent manner. Moreover, prazosin-stimulated HTGL release was suppressed by the PKA inhibitors H-89 and KT5720. These results suggest that prazosin-stimulated HTGL release from hepatocytes was due to cAMP production and partly due to subsequent PKA activation in hepatocytes.