• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Omega-6 for Body, Omega-3 for Brain: Balance for Brain Development in Children (英文原文)

    2022-06-01 10:16:16ThomasBRENNADellMedicalSchoolUniversityofTexasatAustinTX78723UnitedStatesCornellUniversityIthacaNY14853UnitedStates
    糧油食品科技 2022年3期
    關(guān)鍵詞:原文英文

    J. Thomas BRENNA(1. Dell Medical School, University of Texas at Austin, TX 78723, United States;2. Cornell University, Ithaca, NY 14853, United States)

    Abstract: Food must supply a balance of nutrients to support both brain and body. The human brain makes us uniquely human. Essential fatty acids are part of the metabolic pathways that define tissue structure and function. Omega-6 (O6) linoleic acid (LA6) has long been known to be required for skin structure, and as a precursor for inflammatory, thrombotic, immune, and other signaling molecules. Omega-3 (O3) alpha-linolenic acid (ALA3) and particularly its long chain product docosahexaenoic acid (DHA3) has a key structural role in the brain, retina, and related neural tissue. In the 20th century western world, inexpensive, high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development, primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3. Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function. Recent studies emphasize the importance of nutrition to support brain development, with newer findings showing particular importance of fatty acid balance in malnourished children. The World Health Organization (WHO) through the Codex Alimentarius (“Code for Food”) is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition. Similar principles are likely to be important in older persons. Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.

    Key words: brain development; docosahexaenoic acid; Omega-3; Omega-6; high oleic oils; severe acute malnutrition; Ready to use therapeutic food; fatty acid balance

    ABBREVIATIONS

    CVD: Cardiovascular disease

    HUFA: Highly unsaturated fatty acids

    HO: High oleic acid

    PUFA: Polyunsaturated fatty acids

    RUTF: Ready-to-Use Therapeutic Foods

    O6: Omega-6 fatty acids

    LA6: Linoleic acid Omega-6

    ARA6: Arachidonic acid Omega-6

    O3: Omega-3 fatty acids

    ALA3: Alpha-linolenic acid Omega-3

    EPA3: Eicosapentaenoic acid Omega-3

    DHA3: Docosahexaenoic acid Omega-3

    1. INTRODUCTION

    Humans are the animal of the runaway brain[1-2].The human brain is far larger and consumes far more energy as a percent of body weight than any comparably-sized terrestrial animal. In this sense human brains are unique.

    The brains of all mammals have a unique composition compared to all other organs, but brains themselves are similar in their composition. They are dominated by specialized highly unsaturated fatty acids (HUFA), in particular Omega-3 (O3)docosahexaenoic acid (DHA3) and Omega-6 (O6)arachidonic acid (ARA6). This classic observation implies that size of mammalian brains is in some way limited by the ability of the animal to obtain through food the major components of the brain,and specifically DHA3[3].

    Food supplies the essential fatty acids required for all metabolic functions. While the underlying metabolism of fatty acids is similar throughout the body, principles that govern the most obvious aspects of health are different for body and brain.Overt deficiency in the body is avoided with 2% of energy as O6 linoleic acid (LA6) with no O3, even though O3 deficiency causes abnormal development of the brain’s higher functions. Our goal here is to review O6 and O3 nutritional principles with emphasis on recent studies on fatty acid nutrition in brain development of malnourished children.

    2. HUFA SYNTHESIS, BRIEFLY

    We have recently reviewed details of the biochemical pathway and genetics around polyunsaturated fatty acids(PUFA)[4-5]and will summarize key points here.

    The two families of essential fatty acids, PUFA,are supplied in modern diets primarily as LA6 for O6 and alpha-linolenic acid Omega-3 (ALA3) for the O3. These fatty acids are metabolically transformed into the bioactive HUFA by common enzymes coded by common genes (FADS2, FADS1,ELOVL5, ELOVL2), though some evidence shows that alternative transcripts modulate the specificity of the respective enzymes[6]. As a result, the balance between the dietary levels of the main C18 precursors of the two families of PUFA, LA6 and ALA3, are of key importance. The main PUFA/HUFA of importance are as follows, showing that LA6 and ALA3 are primarily precursors for ARA6 and eicosapentaenoic acid Omega-3(EPA3)/DHA3,respectively.

    Omega-6 (O6): LA6→→→ARA6

    Omega-3 (O3): ALA3→→→EPA3→DHA3

    ARA6 is the precursor for more than 100 signaling molecules and appears to be a critical structural component for some neural membranes.DHA3 is required as a structural component of the neural system, and EPA3 is generally required to balance ARA6 signaling.

    3. O6 FOR BODY

    Diets with only LA6 and ALA3 could be achieved with a strict vegan diet, though veganism is a relatively recent practice: few if any ancestral human groups consume no animal products. The vast majority of human diets include HUFA from animal foods (meat and seafood, eggs, dairy) as well as seaplants and some other plants. Endogenous HUFA synthesis is suppressed by dietary HUFA via product inhibition. Recent data also show that many more saturated fatty acids than previously known can affect HUFA biosynthesis[5,7]. Thus, the overall mix of fatty acids in the diet, not only PUFA, affect HUFA synthesis. Nevertheless, concepts such as essential fatty acids, and the “parent” fatty acids were established with rodents primarily on diets with only LA6 and ALA3 and their biology should be understood in that limited context.

    The only known metabolic function of LA6 that, apparently, cannot be satisfied by another fatty acid is as a component of skin lipids. The first known and most prominent symptom of essential fatty acid deficiency is a compromise in the barrier function of skin, leading to skin lesions and pathological evaporation of body water through the skin. While dietary LA6 rapidly cures this condition,so too does dietary ARA6, which is converted to LA6[8]. Moreover, it has long been known that diet ARA6 is more potent for improving skin integrity than diet LA6.

    Diets that have LA6 and little or no ALA3 support growth (weight and length gain) and apparently normal reproduction. These functions can be considered to support the body. Brain function is complex and subtle, and requires careful testing to reveal whether the higher mental functions such as problem solving and balanced mood are normal.Early studies did not test brain function and thus did not detect abnormalities that became obvious in later decades.

    LA6 is special as a dietary FA. Conventional seed oils produced inexpensively and at high quality are generally rich in LA6, for instance soy oil (53%LA6), groundnut (25% LA6), rapeseed (25% LA6)and in the USA, sunflower and safflower oils (70%LA6). These levels compare to, for instance, teaseed oil (10% LA6) and fruit oils olive and palm oil(6%~15% LA6) and animal fats which are in the same low range. Widespread use of high LA6 oils is relatively new. Dietary LA6 suppresses tissue accumulation of all Omega-3 fatty acids, whether ALA3 or HUFA EPA3 and DHA3 by interfering with activation into the biochemical pathways by the acyl coA synthases, inhibiting HUFA biosynthesis,and inhibiting incorporation into tissue. LA6 also accumulates in white adipose to a far greater degree than any O3; this phenomenon is likely to be due to rapid damaging oxidation that O3’s undergo.

    LA6 drives ARA6 levels only up to about 4%of calories (cal)[9]. LA6 levels above about 4% of energy cause levels of the potently bioactive ARA6 to saturate in tissue. Further increases in ARA6 require consumption of preformed dietary ARA6.Most industrialized diets are on average far above 4%en LA6. As a comparison, American LA6 intake is above 10%cal. Halving dietary LA6 from 10% to 5% by substitution with an inert fatty acid (e.g.oleic acid, 18:1n-9) has no effect on circulating ARA6 because ARA6 is already maximal. Levels well below 4%cal are required to see changes.

    4. CIRCULATING FATTY ACID LEVELS AND HEALTH: O3 INDEX AND OTHER FATTY ACIDS

    Among the most reproducible phenomenon in mammalian biochemistry is the competitive nature of dietary fatty acids and specifically LA6 and ALA3. By the early 1960s, feeding studies showed that diets with only LA6 and ALA3 gave highly predicable responses in tissue levels of all PUFA[10-12].These studies have been replicated many times since, and put on a quantitative basis[9,13-15]. The intake of food fatty acids and the genetics of the individual define the composition of tissue and in part its function.

    In recent years laboratory blood tests have been developed to check fatty acid status and potentially recommend dietary changes. The most prominent of these are the O3 tests, though others are likely to emerge.

    Dietary fatty acids and specifically the balance of saturated vs unsaturated fatty acids were considered to influence biomarkers of cardiovascular disease for many decades. Specifically, it is well established that oils rich in LA6 decrease serum cholesterol and LDL-cholesterol. However, LDL’s role as a causal agent in cardiovascular disease, at least at levels below 200 mg/dL (5.2 mmol/L), is complicated by the various types of circulating LDL particles and thus is not straightforward. Substitution of LA6 by saturated fat raises LDL but does not increase cardiovascular disease (CVD) risk[16]. LDL below 200 mg/dL is not a risk factor for CVD in Japan[17].

    Home compatible fatty acid tests are available.In these tests, a drop of blood from a finger prick is collected on treated paper and sealed, and mailed to a testing laboratory. Samples are extracted and analyzed for fatty acids that can be related to disease risk.

    Over the past 15 years, whole blood O3 as a fraction of total PUFA and total HUFA has been developed and validated as a marker of CVD with at least as good predictive power than the cholesterol markers. The HS Omega-3 Index[18]and the Omega-3 HUFA Test[13,19]are examples.

    Many other fatty acids can be reported in the same analyses, including an array of saturated fatty acids, monounsaturated fatty acids, and subset of these such as odd chain fatty acids. Until now these have been used for newborn screening primarily. In adults they are used for research purposes but the data strongly suggest that they will be of importance for individual cases as demand grows for insight into healthy eating practices.

    5. BALANCING O6 AND O3 FOR BODY AND BRAIN

    ALA3 has no known specific metabolic functions that depend upon it, unlike for LA6. Dietary ALA3 is not stored but is rapidly disposed of metabolically by one of three routes: a) oxidation to yield acetate as a carbon source or CO2/H2O as an energy source,b) secretion onto the skin, c) conversion to long chain/more unsaturated PUFA that are required metabolically, specifically DHA3 and EPA3.

    5.1 PUFA balance: excess LA6, not O6/O3 ratio,controls DHA3 levels

    The levels of dietary LA6 and ALA3 influence the transformation of one another to HUFA. It is often said that DHA3 levels are controlled by the dietary ratio of O6 to O3. This is not correct in an important way.

    Many animal[9,20]and human[21-22]studies have shown that circulating and tissue DHA3 is not controlled by the dietary ratio of O6/O3 when only LA6 and ALA3 are the sole sources of the two respective PUFA families. Consider an LA6/ALA3(O6/O3) = 10. If ratio controlled DHA3 levels, then changing the ratio to 5 by either increasing ALA3 two-fold, or reducing LA6 by half, would increase DHA3 levels. The experimental fact is that increasing ALA3 never increases tissue DHA3 while decreasing LA6 increases DHA3. It is therefore more accurate to express the competition between dietary LA6 and ALA3 as one of excess LA6 as inhibitory. Thus,lowering LA6 is required to support DHA3 levels[13].

    6. O3 AND BRAIN DEVELOPMENT THROUGH THE DECADES

    DHA3 was discovered as a component of brain tissue by the 1950s, in the era when nutrition research focused on discovery of vitamins. The main bioactive fatty acid was considered to be LA6 because deficiency of this nutrient was obvious: it led to lesions and compromised the water barrier function of the skin[23]. O3 is not effective in repairing this defect. Looking back, we now know that O3 affects higher brain functions which are not as easily studied as skin lesions. Therefore the essentiality of O3 for human life was not well established until the mid-1980s, decades after O6 essentiality was established[24]. Even now the essentiality of O3 has not been fully corrected across all policy documents.

    6.1 The brain requires O3; DHA3 is likely a required nutrient at least in some lifestages

    It has been known since the 1970s that DHA3 is required to support detection of light in the retina,that is, the visual response[25-28]. About that time,expeditions to the arctic of North America revealed a relationship between high intake of O3 from seafood and low cardiovascular disease, a discovery that caused enormous interest in EPA3 and to a lesser extent DHA3 as a preventative or treatment for cardiovascular disease but did not address O3 as a required nutrient to prevent deficiency symptoms[29-30].

    It was in this decade that O3 deficient diet first appeared, showing that replacement of all fats with an oil with high O6 but negligible O3 in diets of pregnant animals caused deficiency symptoms in rodents[31]. The use and expansion of these diets in the perinatal period for research into O3 expanded later.

    The 1980s showed the first clinical studies of O3 as a key nutrient for brain development. The O3 deficit diet was refined and led to a series of influential papers showing that O3 deficiency caused replacement of DHA3 with the O6 analogue docosapentaenoic acid (DPA6) in rhesus monkeys[32-33].These results matched findings of years earlier in rodents that also reported no changes in growth or reproduction, but looked at no measures of brain development[34]as was indicated by the knowledge that DHA3 accumulates in neural tissue, known for decades and demonstrated systematically for all wild animals a few years later[3]. In contrast,Neuringer and Connor showed that retinal function was dramatically compromised by O3 deficiency,and that retinal function was restored when dietary O3 was restored. A key lesson from this history is that measurements must target the function affected by the agent in question, in this case the growing brain and neural system[35].

    In parallel, the first studies in infants were initiated, showing that the infant formulas of the time, with no DHA3, caused reductions in blood DHA3, similar to those seen in animals[36]. Around this time, reports of fatty acid concentrations in breastmilk using high resolution methods suitable for accurate analysis of DHA appeared and continued to the present[37]. Human clinical studies of the 1980s were concerned with preterm infants and the degree to which dietary preformed DHA3 is needed to maintain DHA3 status[38-41].

    The 1990s were a decade of clinical studies on DHA3 and on O3 deficiency animal models similar to the earlier rhesus monkey studies. Both are too numerous to review here. In total, the clinical studies showed compellingly that preterm infants require preformed DHA3 in feeds while results were judged mixed though nevertheless compelling for term infants[42-43].

    Animal studies of O3 deficiency are of key importance in assessing foods for the general population. By 2011, at least 60 studies of functional outcomes of O3 deficiency appeared[44]. These studies provided diets similar to the rhesus monkey diets and showed that feeding numerous high LA6/low ALA3 oils as the sole source of fat to pregnant animals (rats, mice, pigs, primates) from conception to weaning cause all manner of abnormalities in neural function, from basic biochemical alterations not seen in free living/wild animals, to defects in maze running, visual acuity, neural signal transmission,balance, anxiety, aggression, impulse control, and many other non-neural defects such as abnormalities in circulating catecholamines. As usual, with ample dietary O6, animals grew and reproduced apparently normally though some studies suggested subtle abnormalities in litter size and other non-obvious outcomes (for example, reference [45]).

    These experimental findings lead to a common,perhaps oversimplified but nevertheless accurate rule: omega-6 supports the body, omega-3 supports the brain.

    7. SEVERE ACUTE MALNUTRITION AND PUFA

    Severe acute malnutrition (SAM) caused by lack of food afflicts about 20 million children globally on an annual basis. Rehabilitation from SAM often leaves children with suboptimal mental functioning which can take the form of impaired ability to solve problems or inability to properly regulate mood. Impaired mood consisting of higher levels of depression, anxiety, aggression, as well as indirect risks to mood such as higher sensitivity to pain.

    Therapeutic foods to rehabilitate children from SAM took the form of milks fortified with calories,protein, and micronutrients in the 1990s. Survival(“recovery”) rates were in the range of 50% over a few months post treatment, showing some efficacy but leaving the hypothesis that many more children could be successfully treated.

    7.1 A breakthrough: Ready-to-Use Therapeutic Foods (RUTF)

    Ready-to-Use-Therapeutic Foods (RUTF) were developed around the year 2000[46]. RUTF are based on peanut (groundnut) butter, non-fat dry milk, sugar,vitamins/minerals, and oil, all sealed in a pouch and stable over 2 years at ambient temperature. Survival rates increased to over 90% by 2007, a major success that provides a suitable treatment for most malnourished children.

    7.2 From survive to thrive

    In human development, life-threatening conditions are first approached by the search for methods that enable survival. Once a treatment is found, research pediatricians turn attention to long term effects so to optimize the ability to live and thrive in the long term.

    As with the story of preterm infants, the well-established human biology of PUFA nutrition was not a focus. And as with preterm infants, it was the O3 fatty acids that were of concern, though for different reasons. With preterm infants, the key issue was the inclusion of DHA3 in artificial feeds to parallel the composition of human milk more accurately.

    With RUTF, the key issue was the use of oils with overwhelming amounts of LA6, as well as the lack of DHA3. This oversight was at least in part due to (a) the supply of vegetable oils available as ingredients for making RUTF, and (b) the lack of emphasis in global food standards for the interactions of nutrients within a diet, that is, that the level of one nutrient affects the requirements for the other.For RUTF, it was the high level of LA6 that causes a metabolic demand for all O3 by antagonizing O3 accretion in all tissues. Conventional peanuts, the main ingredient in RUTF, are high fat and contain high LA6 and no ALA3. Oils added to increase calorie content and with it, add some ALA3, were even higher in LA6 (for example, soy) and though they increased ALA3 they increased LA6 by more.

    A 2010 conference in California brought together specialists in fatty acid nutrition and in malnutrition to consider aspects of PUFA nutrition.Emerging from that event was a collaborative team that established that, in fact, RUTF using the customary recipe could not achieve even modest ratio of LA6 to ALA3 (O6/O3) < 10 that was expected by the World Health Organization recommendations. Importantly some of the RUTF in use at that time had compositions similar to the O3-deficit diets that caused permanent neurological impairment in animal studies.

    7.3 A smarter food for long term benefits

    The availability of high oleic (HO) peanuts[47]opened the possibility to reformulate RUTF with oils that have lower levels of LA6 that will minimally antagonize O3. The most common HO oil in the west is olive oil which contains around 10% LA6 and over 80% oleic acid, with little ALA3 and no DHA3 or EPA3. This composition is similar to teaseed oil available in China. Early studies have shown that very low levels of dietary LA6 are needed to avoid deficiency symptoms[48], and that amounts above the minimum create a metabolic demand for DHA3[24]. The basic problem is that mosttraditionalcommercial oils, such as rapeseed,soy, sesame, contain high amounts of LA6 and low or zero O3. HO oils developed by traditional plant breeding, without artificial genetic modification,have a composition similar to olive and teaseed oil.HO peanut with their low LA6 and high oil content are a solution to the problem of high LA6 oils creating a metabolic demand for DHA3.

    Studies in animals show that even extreme amounts of dietary ALA3 as the only source of O3 do not support tissue DHA3 in all neural tissue at the same levels as dietary preformed DHA3[49].Even with HO oils and lower LA6, DHA3 may not reach the same levels as with preformed DHA3 in the diet. On this basis, we cast the hypothesis that RUTF with HO peanuts (lower LA6), and fortified with a modest amount of DHA3 would better support tissue levels of DHA3.

    In our first study, we tested the hypothesis in a group of 81 children of mean age about 2 years and diagnosed with SAM in Malawi. We used only control and HO RUTF for a period of 4~12 weeks until body recovery was found. In four weeks,circulating phospholipid DHA3 dramatically decreased a stunning 25% on the control RUTF with 26% LA6 and <1% ALA3 (% by weight of fatty acids). In the HO diet with 13% LA6 and ALA3,DHA3 stabilized, showing that with balance the children could make sufficient DHA3 to supply tissue needs as the flood of calories and protein from RUTF were available to restart brain growth[50].A similar study in a smaller number of children conducted by other researchers in Kenya that did not decrease LA6 but added ALA3 showed a non-significant decrease in DHA3[51]. This paper highlighted the importance of controlling LA6 levels and led to modest changes in RUTF composition.

    Our most recent study was designed to evaluate brain function in over 1 000 children of 2 800 in the study[52]. The three groups received RUTF of various PUFA compositions: Control, HO formulated with HO peanuts with low LA6, and DHA-HO with added DHA (Table 1). Recovery of the body from malnutrition was similar in all groups as assessed by arm circumference. Children went home for six months and then their mental function was tested by the Malawi Developmental Aptitude Test. Compared to Control RUTF, the children receiving DHA3-HO RUTF performed significantly better six months after completing treatment with no intervention during the time away (Figure 1). Though the HO RUTF was not overall significantly improved, the trend to improvement was apparent in all components of the testing, and the social score was the highest in HO RUTF group.

    Table 1 RUTF PUFA composition from[50]

    Fig.1 Long term mental function

    Thus, in the long term, six months post treatment with no intervention, the DHA-HO RUTF supported superior brain function, with most significant effects in the gross motor and social domains.

    8. CONCLUSIONS: WHO RECOMMENDATIONS AND IMPLICATIONS

    The World Health Organization Codex Alimentarius meets annually in November to consider recommendations for composition of foods. The process for considering proposed recommendations is highly structured, inviting input from country delegates worldwide. The responsible 2021 Codex committee finalized recommendations[53]for the composition of RUTF in part based on our findings in Malawi. Maximal LA6 was set at 780 mg and minimum ALA was set at 110 mg per 100 kcal,compromise levels proposed prior to the time our study[52]appeared. These recommendations are a major improvement over the previous proposed higher LA6 and lower ALA3 levels. DHA3 addition is permitted and is being added to RUTFs by some manufacturers.

    The emphasis on brain development reflected by the unanimous action of Codex may represent a change in attitude toward brain health in general.Malnourished children are among the vulnerable populations, but these results translate to all populations and life stages even if the effects on calorie/protein-replete children/adults/elderly are smaller. In this author’s opinion, research should emphasize development of the organ that makes us human, the brain, and body health will follow.

    ACKNOWLEDGEMENTS

    Basic research on fatty acids was generously supported by numerous US NIH grants to the author(R01s AT007003, GM103437, GM71534, EY10208,GM49209). The 2021 research in Malawi was generously funded by Unorthodox Philanthropy,Open Philanthropy, the Hickey Family Foundation,and the Children’s Discovery Institute, and Wiley Companies supported the work with a donation of ingredients for one of the study foods. The author is grateful for the collegial collaboration of Mark Manary and the team at Washington University in St Louis (WashU), and of Andre Briend.

    猜你喜歡
    原文英文
    讓句子動(dòng)起來
    英文摘要
    英文摘要
    英文摘要
    英文摘要
    英文摘要
    英文摘要
    嘗糞憂心
    扼虎救父
    恣蚊飽血
    日本一本二区三区精品| 国产亚洲精品av在线| 国产成人aa在线观看| av女优亚洲男人天堂| www.熟女人妻精品国产| 亚洲成av人片在线播放无| 欧美日韩黄片免| 婷婷六月久久综合丁香| www.999成人在线观看| 欧美zozozo另类| 一区二区三区免费毛片| 欧美zozozo另类| 综合色av麻豆| 99久久无色码亚洲精品果冻| 深爱激情五月婷婷| 亚洲熟妇中文字幕五十中出| 欧美bdsm另类| 无遮挡黄片免费观看| 亚洲成人精品中文字幕电影| av欧美777| 色噜噜av男人的天堂激情| 18禁国产床啪视频网站| 97超视频在线观看视频| 国产精品一区二区三区四区久久| 亚洲av免费在线观看| 国产欧美日韩精品亚洲av| 99精品欧美一区二区三区四区| 午夜免费观看网址| 欧美在线一区亚洲| 法律面前人人平等表现在哪些方面| 国产免费男女视频| 精品久久久久久,| 九九热线精品视视频播放| 成年人黄色毛片网站| 国产高清videossex| 国产精品99久久99久久久不卡| 亚洲精品成人久久久久久| 深爱激情五月婷婷| 婷婷丁香在线五月| 欧美最新免费一区二区三区 | 亚洲中文字幕日韩| 中文字幕人成人乱码亚洲影| 国产精品女同一区二区软件 | 亚洲五月婷婷丁香| 亚洲人成网站高清观看| 我的老师免费观看完整版| 在线免费观看的www视频| 欧美成人一区二区免费高清观看| 国产又黄又爽又无遮挡在线| 不卡一级毛片| 国产精品三级大全| 久99久视频精品免费| 国内精品久久久久精免费| 色老头精品视频在线观看| 国产探花在线观看一区二区| 国产黄色小视频在线观看| 哪里可以看免费的av片| 一二三四社区在线视频社区8| 久久久成人免费电影| 精品国产美女av久久久久小说| 男人舔奶头视频| 午夜影院日韩av| 在线视频色国产色| 久久精品国产自在天天线| 搡老岳熟女国产| 成人国产一区最新在线观看| av中文乱码字幕在线| 女人高潮潮喷娇喘18禁视频| 日韩欧美精品v在线| 色噜噜av男人的天堂激情| 床上黄色一级片| 欧美在线一区亚洲| 三级毛片av免费| 亚洲第一电影网av| 两个人的视频大全免费| 综合色av麻豆| 久久草成人影院| 老司机深夜福利视频在线观看| 亚洲美女黄片视频| av视频在线观看入口| 久久草成人影院| av专区在线播放| 欧美激情久久久久久爽电影| 少妇人妻一区二区三区视频| 十八禁网站免费在线| 男人的好看免费观看在线视频| 中文字幕人妻熟人妻熟丝袜美 | 色播亚洲综合网| 亚洲avbb在线观看| 熟女电影av网| 久久香蕉国产精品| 国产69精品久久久久777片| 欧美日韩国产亚洲二区| avwww免费| 嫩草影院入口| 九色国产91popny在线| 日本黄色视频三级网站网址| 综合色av麻豆| 蜜桃久久精品国产亚洲av| 国产精品自产拍在线观看55亚洲| 国产单亲对白刺激| 老司机在亚洲福利影院| 岛国视频午夜一区免费看| 亚洲国产色片| 搡老熟女国产l中国老女人| 亚洲精品日韩av片在线观看 | 精品久久久久久久人妻蜜臀av| 91字幕亚洲| 淫秽高清视频在线观看| 婷婷丁香在线五月| 精品不卡国产一区二区三区| 床上黄色一级片| 非洲黑人性xxxx精品又粗又长| 久久精品国产综合久久久| 国产男靠女视频免费网站| 我要搜黄色片| 亚洲avbb在线观看| 成人av一区二区三区在线看| 天天添夜夜摸| 人妻久久中文字幕网| 一个人看的www免费观看视频| 久久精品国产亚洲av香蕉五月| a在线观看视频网站| 久久人妻av系列| 色哟哟哟哟哟哟| 久久久久久大精品| 中出人妻视频一区二区| 亚洲成人免费电影在线观看| АⅤ资源中文在线天堂| 两人在一起打扑克的视频| 午夜精品一区二区三区免费看| 99久久无色码亚洲精品果冻| 免费大片18禁| 一级作爱视频免费观看| 精品日产1卡2卡| 精品久久久久久久人妻蜜臀av| 日本黄大片高清| 伊人久久大香线蕉亚洲五| 波多野结衣高清作品| 成人无遮挡网站| 一级作爱视频免费观看| 国产色婷婷99| 国产精品一区二区三区四区免费观看 | 少妇裸体淫交视频免费看高清| 国产成人av教育| 欧美国产日韩亚洲一区| xxx96com| 97碰自拍视频| 男女视频在线观看网站免费| 免费人成在线观看视频色| 嫩草影视91久久| 日韩欧美免费精品| 久久人妻av系列| 久久精品人妻少妇| 母亲3免费完整高清在线观看| 亚洲精品乱码久久久v下载方式 | 午夜福利成人在线免费观看| 不卡一级毛片| 天天添夜夜摸| www.熟女人妻精品国产| 国产av在哪里看| 欧美成人性av电影在线观看| 日韩大尺度精品在线看网址| 国产精品影院久久| 国模一区二区三区四区视频| 免费人成在线观看视频色| 亚洲美女黄片视频| 精品欧美国产一区二区三| 人人妻人人看人人澡| av天堂在线播放| 69av精品久久久久久| 国产精品永久免费网站| 国产免费男女视频| 亚洲真实伦在线观看| 搞女人的毛片| 99久国产av精品| 国产成人av激情在线播放| 又黄又爽又免费观看的视频| 在线视频色国产色| 日本 欧美在线| 蜜桃久久精品国产亚洲av| 国产亚洲精品综合一区在线观看| 国产乱人视频| 在线免费观看的www视频| 亚洲av一区综合| 1024手机看黄色片| 成人18禁在线播放| 久久精品亚洲精品国产色婷小说| 久久香蕉精品热| 在线天堂最新版资源| 亚洲成人中文字幕在线播放| 九九久久精品国产亚洲av麻豆| 嫩草影院精品99| 18禁黄网站禁片午夜丰满| 日本在线视频免费播放| 国产av麻豆久久久久久久| 激情在线观看视频在线高清| 国产av在哪里看| 日韩欧美一区二区三区在线观看| 亚洲性夜色夜夜综合| 母亲3免费完整高清在线观看| 97超级碰碰碰精品色视频在线观看| 高清在线国产一区| 中文字幕久久专区| 国产亚洲精品久久久久久毛片| 亚洲乱码一区二区免费版| 天天添夜夜摸| 51国产日韩欧美| 老师上课跳d突然被开到最大视频 久久午夜综合久久蜜桃 | 久久性视频一级片| 一卡2卡三卡四卡精品乱码亚洲| 国产精品一区二区三区四区免费观看 | 99国产极品粉嫩在线观看| 一个人观看的视频www高清免费观看| 久久久久久久亚洲中文字幕 | 99国产综合亚洲精品| 色尼玛亚洲综合影院| 色哟哟哟哟哟哟| 乱人视频在线观看| 精品一区二区三区av网在线观看| 久久99热这里只有精品18| 叶爱在线成人免费视频播放| 一级毛片女人18水好多| 久久精品夜夜夜夜夜久久蜜豆| 国产欧美日韩一区二区精品| 又黄又粗又硬又大视频| 国产精品久久久人人做人人爽| 黄色片一级片一级黄色片| 少妇熟女aⅴ在线视频| 亚洲片人在线观看| 中国美女看黄片| 久久人妻av系列| 婷婷精品国产亚洲av| www日本黄色视频网| 欧美成人性av电影在线观看| 欧美国产日韩亚洲一区| 国产午夜福利久久久久久| 19禁男女啪啪无遮挡网站| 毛片女人毛片| 午夜久久久久精精品| 国产精品国产高清国产av| 黄色女人牲交| 国产亚洲av嫩草精品影院| 99久久99久久久精品蜜桃| 亚洲精品成人久久久久久| 91久久精品国产一区二区成人 | 一进一出抽搐gif免费好疼| 国产精品一区二区三区四区久久| 国产真实乱freesex| 国产成人av激情在线播放| 一区二区三区高清视频在线| 亚洲精品粉嫩美女一区| 好男人在线观看高清免费视频| 黑人欧美特级aaaaaa片| 天天一区二区日本电影三级| 日韩 欧美 亚洲 中文字幕| 欧美一区二区亚洲| 最新在线观看一区二区三区| 成人18禁在线播放| 一个人看的www免费观看视频| 欧美+亚洲+日韩+国产| 88av欧美| 久久久色成人| 欧美日本视频| 精品久久久久久,| 观看美女的网站| x7x7x7水蜜桃| 小蜜桃在线观看免费完整版高清| 亚洲自拍偷在线| 51午夜福利影视在线观看| 久久草成人影院| 国产老妇女一区| 国产欧美日韩精品亚洲av| 最新在线观看一区二区三区| 国产精品乱码一区二三区的特点| 亚洲精品在线观看二区| 美女cb高潮喷水在线观看| 国产熟女xx| 免费看a级黄色片| 日韩av在线大香蕉| 真实男女啪啪啪动态图| 国内少妇人妻偷人精品xxx网站| 一个人免费在线观看的高清视频| 国产精品久久久久久久久免 | 青草久久国产| 最近最新中文字幕大全电影3| 黄色日韩在线| 午夜免费观看网址| 国产成人影院久久av| 黑人欧美特级aaaaaa片| 亚洲 国产 在线| 色综合站精品国产| 久久草成人影院| 亚洲中文字幕日韩| 成年女人永久免费观看视频| 国产亚洲欧美98| 日韩精品中文字幕看吧| 日韩欧美一区二区三区在线观看| 最近在线观看免费完整版| 免费在线观看日本一区| 亚洲精品在线美女| 成年女人永久免费观看视频| www国产在线视频色| 熟女电影av网| 国产精品女同一区二区软件 | 18禁在线播放成人免费| 亚洲av电影不卡..在线观看| 精华霜和精华液先用哪个| 亚洲欧美日韩高清专用| 人妻夜夜爽99麻豆av| 国产高清有码在线观看视频| 国产亚洲精品一区二区www| АⅤ资源中文在线天堂| 欧美最黄视频在线播放免费| 亚洲,欧美精品.| 欧美极品一区二区三区四区| 成人三级黄色视频| 欧美色欧美亚洲另类二区| 日韩人妻高清精品专区| 99在线视频只有这里精品首页| 一区二区三区激情视频| 给我免费播放毛片高清在线观看| 久久国产精品影院| 69av精品久久久久久| 久久精品国产亚洲av涩爱 | 97超级碰碰碰精品色视频在线观看| 老熟妇仑乱视频hdxx| 日韩高清综合在线| 在线观看66精品国产| 色播亚洲综合网| 国产精品乱码一区二三区的特点| 日日干狠狠操夜夜爽| 在线播放无遮挡| 成人特级av手机在线观看| 观看免费一级毛片| 五月玫瑰六月丁香| 脱女人内裤的视频| 国产伦精品一区二区三区视频9 | 婷婷精品国产亚洲av在线| 男人的好看免费观看在线视频| 一级黄色大片毛片| 母亲3免费完整高清在线观看| 国内精品一区二区在线观看| 最近最新中文字幕大全免费视频| 搞女人的毛片| 欧美zozozo另类| 少妇熟女aⅴ在线视频| 午夜亚洲福利在线播放| 久久久久国产精品人妻aⅴ院| 18禁美女被吸乳视频| 91在线观看av| 一个人免费在线观看电影| 可以在线观看毛片的网站| 深夜精品福利| 久久久久久久亚洲中文字幕 | 1024手机看黄色片| 国产爱豆传媒在线观看| 精品无人区乱码1区二区| 嫩草影视91久久| 少妇人妻精品综合一区二区 | av国产免费在线观看| 亚洲精品456在线播放app | 每晚都被弄得嗷嗷叫到高潮| 热99在线观看视频| 精品久久久久久成人av| 久久99热这里只有精品18| 日本在线视频免费播放| 久久中文看片网| 日本在线视频免费播放| 国产精品免费一区二区三区在线| 真实男女啪啪啪动态图| 国产欧美日韩精品亚洲av| 免费观看精品视频网站| 一二三四社区在线视频社区8| 国产精品永久免费网站| 国产伦精品一区二区三区视频9 | 一区福利在线观看| 欧洲精品卡2卡3卡4卡5卡区| 黄色女人牲交| 两个人看的免费小视频| www.999成人在线观看| 亚洲人成网站高清观看| 变态另类丝袜制服| 亚洲成av人片在线播放无| 亚洲性夜色夜夜综合| 香蕉久久夜色| 搡老妇女老女人老熟妇| 久久久久国产精品人妻aⅴ院| 久久久久久久精品吃奶| 婷婷精品国产亚洲av| 一区二区三区免费毛片| 国产一级毛片七仙女欲春2| 国产亚洲精品久久久com| 身体一侧抽搐| 亚洲成人久久爱视频| 91字幕亚洲| 亚洲人成伊人成综合网2020| 美女大奶头视频| 99久国产av精品| 五月伊人婷婷丁香| 精品久久久久久久久久久久久| 宅男免费午夜| 嫩草影视91久久| 欧美成人a在线观看| 欧美另类亚洲清纯唯美| 国产三级在线视频| 久久久色成人| 午夜福利在线观看免费完整高清在 | 一边摸一边抽搐一进一小说| 中文亚洲av片在线观看爽| 国产亚洲精品久久久com| 每晚都被弄得嗷嗷叫到高潮| 在线看三级毛片| ponron亚洲| 无人区码免费观看不卡| 最好的美女福利视频网| 精品99又大又爽又粗少妇毛片 | 村上凉子中文字幕在线| 精品99又大又爽又粗少妇毛片 | 两个人的视频大全免费| 高清毛片免费观看视频网站| 麻豆一二三区av精品| 老汉色av国产亚洲站长工具| 国产精品久久久久久久久免 | 午夜福利成人在线免费观看| 2021天堂中文幕一二区在线观| 久久久国产成人免费| 久久国产精品影院| 性色av乱码一区二区三区2| 淫妇啪啪啪对白视频| 欧美一区二区精品小视频在线| 日韩高清综合在线| 老熟妇乱子伦视频在线观看| 香蕉丝袜av| 麻豆一二三区av精品| 欧美黄色片欧美黄色片| 熟女少妇亚洲综合色aaa.| 日本免费a在线| 国产中年淑女户外野战色| 国产午夜福利久久久久久| 国产精品久久视频播放| 岛国在线观看网站| 日本免费a在线| 久久精品国产综合久久久| 成年女人永久免费观看视频| 欧美一级a爱片免费观看看| 亚洲,欧美精品.| 九色国产91popny在线| 日韩 欧美 亚洲 中文字幕| 最新在线观看一区二区三区| 国产av在哪里看| 亚洲成a人片在线一区二区| 91久久精品电影网| 欧美精品啪啪一区二区三区| 午夜a级毛片| 国产视频内射| 又粗又爽又猛毛片免费看| 免费观看的影片在线观看| 日本熟妇午夜| 亚洲无线在线观看| 色尼玛亚洲综合影院| 在线观看一区二区三区| 亚洲人与动物交配视频| 精品国产亚洲在线| 久久久久国内视频| 少妇高潮的动态图| 亚洲av熟女| 国产探花极品一区二区| 亚洲性夜色夜夜综合| 精品久久久久久久人妻蜜臀av| 免费高清视频大片| 99热这里只有是精品50| 在线免费观看的www视频| 国产精品永久免费网站| 午夜a级毛片| 国产精品99久久99久久久不卡| 制服丝袜大香蕉在线| 757午夜福利合集在线观看| 久久天躁狠狠躁夜夜2o2o| 日本黄色视频三级网站网址| 非洲黑人性xxxx精品又粗又长| 国产真人三级小视频在线观看| 亚洲不卡免费看| 午夜免费观看网址| 在线国产一区二区在线| 岛国在线免费视频观看| 国产亚洲精品久久久久久毛片| 亚洲人与动物交配视频| 在线观看一区二区三区| 99热精品在线国产| 亚洲精品国产精品久久久不卡| 国产探花极品一区二区| 国产亚洲精品久久久com| 精品人妻1区二区| 特大巨黑吊av在线直播| 丰满的人妻完整版| 在线国产一区二区在线| 亚洲七黄色美女视频| 三级男女做爰猛烈吃奶摸视频| 1024手机看黄色片| 村上凉子中文字幕在线| 国产 一区 欧美 日韩| 露出奶头的视频| h日本视频在线播放| 男人和女人高潮做爰伦理| 悠悠久久av| 久久草成人影院| 亚洲av免费在线观看| 欧美乱码精品一区二区三区| 亚洲aⅴ乱码一区二区在线播放| h日本视频在线播放| 欧美性感艳星| 精品不卡国产一区二区三区| 国内精品久久久久久久电影| 国产高清激情床上av| 日日摸夜夜添夜夜添小说| 最近最新中文字幕大全免费视频| 老汉色∧v一级毛片| 成年女人毛片免费观看观看9| 国产欧美日韩一区二区三| 亚洲中文日韩欧美视频| 免费搜索国产男女视频| 日韩免费av在线播放| 欧美3d第一页| 他把我摸到了高潮在线观看| 在线播放无遮挡| 亚洲精品久久国产高清桃花| 91字幕亚洲| 亚洲不卡免费看| 欧美日韩中文字幕国产精品一区二区三区| 欧美日韩精品网址| 黄色片一级片一级黄色片| 搡女人真爽免费视频火全软件 | h日本视频在线播放| 久99久视频精品免费| 五月伊人婷婷丁香| 久久久精品大字幕| 欧美成人性av电影在线观看| 国产高清视频在线播放一区| 性欧美人与动物交配| 搡女人真爽免费视频火全软件 | 国产伦精品一区二区三区视频9 | 欧美黄色片欧美黄色片| 国产精品99久久久久久久久| 欧美乱妇无乱码| 欧美一区二区精品小视频在线| 一级黄片播放器| 1000部很黄的大片| 亚洲精品一区av在线观看| 国产精品美女特级片免费视频播放器| 免费在线观看影片大全网站| 熟女人妻精品中文字幕| 日韩免费av在线播放| 欧美3d第一页| 国产主播在线观看一区二区| 精品久久久久久久久久免费视频| 色综合站精品国产| 激情在线观看视频在线高清| 18禁美女被吸乳视频| 小说图片视频综合网站| 国产淫片久久久久久久久 | 国产高清三级在线| 国产高清视频在线观看网站| 亚洲在线自拍视频| 黄色视频,在线免费观看| 亚洲国产高清在线一区二区三| 国产成人欧美在线观看| 天堂动漫精品| 日韩国内少妇激情av| 国产淫片久久久久久久久 | 亚洲熟妇熟女久久| 国语自产精品视频在线第100页| 国产麻豆成人av免费视频| 一进一出好大好爽视频| 欧美+日韩+精品| 给我免费播放毛片高清在线观看| eeuss影院久久| 国产激情欧美一区二区| 中亚洲国语对白在线视频| 此物有八面人人有两片| 99久久成人亚洲精品观看| 超碰av人人做人人爽久久 | 国产精品 国内视频| 99国产极品粉嫩在线观看| 亚洲人成网站高清观看| 久久久久久久精品吃奶| 神马国产精品三级电影在线观看| 国产在视频线在精品| 18禁在线播放成人免费| 国产精品国产高清国产av| 国产成人影院久久av| 大型黄色视频在线免费观看| 日本一二三区视频观看| 国产精品 欧美亚洲| 草草在线视频免费看| 国产高清三级在线| 国产精品三级大全| 久久精品亚洲精品国产色婷小说| 最近最新中文字幕大全免费视频| 又紧又爽又黄一区二区| 18禁黄网站禁片午夜丰满| 国产成人系列免费观看| 精品人妻一区二区三区麻豆 | 国内揄拍国产精品人妻在线| 日本一本二区三区精品| or卡值多少钱| 看免费av毛片| 999久久久精品免费观看国产| 精品欧美国产一区二区三| 国产真实伦视频高清在线观看 | 男人舔女人下体高潮全视频| 99热这里只有是精品50| 国产精品日韩av在线免费观看| 脱女人内裤的视频| 国产黄色小视频在线观看|