• <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
    av专区在线播放| 亚洲成a人片在线一区二区| 男插女下体视频免费在线播放| 嫩草影院新地址| 国产成人福利小说| 成人国产麻豆网| 男女下面进入的视频免费午夜| 久久精品国产自在天天线| 免费不卡的大黄色大毛片视频在线观看 | 精品人妻视频免费看| 波多野结衣高清作品| 免费搜索国产男女视频| 中出人妻视频一区二区| 色5月婷婷丁香| 日韩人妻高清精品专区| 亚洲av日韩精品久久久久久密| 毛片女人毛片| 亚洲图色成人| 国产精品一区二区三区四区免费观看 | 久久国产乱子免费精品| 最近中文字幕高清免费大全6 | 12—13女人毛片做爰片一| 免费不卡的大黄色大毛片视频在线观看 | 99在线视频只有这里精品首页| 级片在线观看| 亚洲精品一卡2卡三卡4卡5卡| 色噜噜av男人的天堂激情| 日韩欧美免费精品| 99久国产av精品| 尾随美女入室| 欧美又色又爽又黄视频| 俄罗斯特黄特色一大片| 男人狂女人下面高潮的视频| 亚洲国产精品合色在线| 精品国产三级普通话版| 成人无遮挡网站| 欧美高清性xxxxhd video| 亚洲欧美日韩东京热| 午夜福利18| 国产精品自产拍在线观看55亚洲| 欧美xxxx性猛交bbbb| 成人一区二区视频在线观看| 1000部很黄的大片| 久久久精品欧美日韩精品| 少妇人妻精品综合一区二区 | 国产中年淑女户外野战色| 美女被艹到高潮喷水动态| 一进一出抽搐gif免费好疼| 国产男人的电影天堂91| 亚洲人与动物交配视频| 尾随美女入室| 亚洲欧美日韩无卡精品| 欧美激情在线99| 亚洲avbb在线观看| 中文亚洲av片在线观看爽| 色综合亚洲欧美另类图片| 性插视频无遮挡在线免费观看| 一卡2卡三卡四卡精品乱码亚洲| 国产精品乱码一区二三区的特点| 黄片wwwwww| 国产av不卡久久| 成人特级av手机在线观看| 国产91精品成人一区二区三区| 欧美色欧美亚洲另类二区| 精品欧美国产一区二区三| 真实男女啪啪啪动态图| 国产一级毛片七仙女欲春2| 美女黄网站色视频| 欧美色视频一区免费| 亚洲在线自拍视频| 国产精品99久久久久久久久| 在线观看免费视频日本深夜| 欧美又色又爽又黄视频| 搡女人真爽免费视频火全软件 | 亚洲国产高清在线一区二区三| 国内精品美女久久久久久| 午夜免费成人在线视频| 午夜亚洲福利在线播放| 真人做人爱边吃奶动态| 久久欧美精品欧美久久欧美| а√天堂www在线а√下载| 国产中年淑女户外野战色| 久久精品国产亚洲网站| 亚洲精品亚洲一区二区| 午夜福利在线观看免费完整高清在 | 一进一出抽搐gif免费好疼| 免费在线观看影片大全网站| 国产一级毛片七仙女欲春2| 日韩欧美 国产精品| 国产蜜桃级精品一区二区三区| 亚洲av日韩精品久久久久久密| 亚洲av免费高清在线观看| xxxwww97欧美| 男人狂女人下面高潮的视频| av在线老鸭窝| 内射极品少妇av片p| 99视频精品全部免费 在线| 亚洲专区中文字幕在线| 自拍偷自拍亚洲精品老妇| 男人舔女人下体高潮全视频| 国产精品一区二区三区四区久久| 精品乱码久久久久久99久播| 亚洲av一区综合| 午夜老司机福利剧场| 真人一进一出gif抽搐免费| 91麻豆av在线| 在线观看舔阴道视频| 亚洲国产精品合色在线| 国产爱豆传媒在线观看| 亚洲自偷自拍三级| 国产成人福利小说| 精品久久久久久久末码| 可以在线观看的亚洲视频| 欧美日韩亚洲国产一区二区在线观看| 久久久精品大字幕| 伦精品一区二区三区| 免费av不卡在线播放| 黄片wwwwww| 亚洲精品国产成人久久av| or卡值多少钱| 韩国av在线不卡| 干丝袜人妻中文字幕| 中文字幕久久专区| 亚洲欧美日韩东京热| 无遮挡黄片免费观看| 亚洲国产欧洲综合997久久,| 一个人免费在线观看电影| 国产精华一区二区三区| 国产大屁股一区二区在线视频| 成人永久免费在线观看视频| 国产精品久久久久久久电影| 人人妻人人澡欧美一区二区| 五月玫瑰六月丁香| 国产黄色小视频在线观看| 成人二区视频| 亚洲av五月六月丁香网| 99在线人妻在线中文字幕| 少妇人妻精品综合一区二区 | 99久久精品国产国产毛片| 99精品在免费线老司机午夜| 国产精品久久久久久亚洲av鲁大| 亚洲七黄色美女视频| 九九爱精品视频在线观看| 成年女人看的毛片在线观看| 色综合站精品国产| 欧美成人免费av一区二区三区| 亚洲经典国产精华液单| 波多野结衣高清作品| 国内精品久久久久久久电影| 婷婷亚洲欧美| 精品午夜福利在线看| 国产成人aa在线观看| 欧美日本视频| 热99在线观看视频| 国产美女午夜福利| 国语自产精品视频在线第100页| 免费电影在线观看免费观看| 国产69精品久久久久777片| 日本熟妇午夜| 国产私拍福利视频在线观看| 国产亚洲欧美98| 亚洲国产精品合色在线| 国产一区二区亚洲精品在线观看| 成人二区视频| 永久网站在线| 18禁在线播放成人免费| 天堂网av新在线| 此物有八面人人有两片| 午夜老司机福利剧场| 国产精品野战在线观看| 国产精品久久久久久精品电影| 制服丝袜大香蕉在线| 又爽又黄无遮挡网站| 18+在线观看网站| 亚洲,欧美,日韩| 国内少妇人妻偷人精品xxx网站| 国产精品人妻久久久影院| 天天躁日日操中文字幕| 久久国内精品自在自线图片| 亚洲一区高清亚洲精品| 淫妇啪啪啪对白视频| 一级黄色大片毛片| 色在线成人网| 亚洲国产欧洲综合997久久,| 久久天躁狠狠躁夜夜2o2o| 狂野欧美白嫩少妇大欣赏| 又黄又爽又刺激的免费视频.| 国产精品一区二区三区四区免费观看 | 久久久久久伊人网av| 99精品久久久久人妻精品| 尾随美女入室| 在线免费观看的www视频| 久9热在线精品视频| 色5月婷婷丁香| 国产私拍福利视频在线观看| 久久精品国产亚洲网站| 国产一区二区三区视频了| 听说在线观看完整版免费高清| 直男gayav资源| 97碰自拍视频| 国模一区二区三区四区视频| 国产精品亚洲美女久久久| 99热网站在线观看| 久久久国产成人精品二区| 日本黄色视频三级网站网址| 精品免费久久久久久久清纯| 小蜜桃在线观看免费完整版高清| 国产精品,欧美在线| 国产日本99.免费观看| 国产精品1区2区在线观看.| 亚洲精品粉嫩美女一区| 在线播放国产精品三级| 亚洲成人精品中文字幕电影| av女优亚洲男人天堂| 国产精品乱码一区二三区的特点| 久久久久久大精品| 日本一本二区三区精品| 成人国产麻豆网| bbb黄色大片| 国产黄片美女视频| 有码 亚洲区| 校园春色视频在线观看| 亚洲乱码一区二区免费版| 最后的刺客免费高清国语| 在线观看舔阴道视频| 精品乱码久久久久久99久播| 亚洲美女搞黄在线观看 | 亚洲无线在线观看| 国产成人a区在线观看| 午夜福利18| 男人和女人高潮做爰伦理| 欧美激情国产日韩精品一区| 久久久久久国产a免费观看| 日本三级黄在线观看| 欧美又色又爽又黄视频| 国产精品嫩草影院av在线观看 | 综合色av麻豆| 中文字幕人妻熟人妻熟丝袜美| 国产三级在线视频| 人妻少妇偷人精品九色| 夜夜看夜夜爽夜夜摸| 天美传媒精品一区二区| 日韩欧美在线乱码| 欧美日韩瑟瑟在线播放| 日本-黄色视频高清免费观看| 一级a爱片免费观看的视频| 欧美日韩中文字幕国产精品一区二区三区| 免费搜索国产男女视频| 老司机福利观看| 天天一区二区日本电影三级| 精品人妻1区二区| 99热只有精品国产| 午夜老司机福利剧场| 久久精品国产亚洲av天美| 亚洲av五月六月丁香网| 久久精品综合一区二区三区| 亚洲在线观看片| avwww免费| 99精品久久久久人妻精品| 欧美日韩国产亚洲二区| 亚洲美女黄片视频| 日日干狠狠操夜夜爽| 啦啦啦啦在线视频资源| 中文资源天堂在线| 国产三级在线视频| 免费人成视频x8x8入口观看| 天堂影院成人在线观看| 亚洲美女视频黄频| 婷婷丁香在线五月| 久久久午夜欧美精品| 国模一区二区三区四区视频| 色综合色国产| 极品教师在线免费播放| 麻豆一二三区av精品| 香蕉av资源在线| 如何舔出高潮| 此物有八面人人有两片| 18禁黄网站禁片午夜丰满| 亚洲国产高清在线一区二区三| 女人十人毛片免费观看3o分钟| 午夜日韩欧美国产| 国产国拍精品亚洲av在线观看| 久久精品国产鲁丝片午夜精品 | 九九爱精品视频在线观看| 午夜影院日韩av| 能在线免费观看的黄片| 国产一区二区三区视频了| 嫩草影院入口| 欧美日韩瑟瑟在线播放| 一夜夜www| 亚洲av中文字字幕乱码综合| 有码 亚洲区| 真实男女啪啪啪动态图| 国产91精品成人一区二区三区| 成熟少妇高潮喷水视频| 深夜a级毛片| 国产精品一区www在线观看 | 免费看av在线观看网站| 精品人妻1区二区| 在线免费十八禁| 欧美日韩综合久久久久久 | 波多野结衣巨乳人妻| 免费电影在线观看免费观看| 一本精品99久久精品77| 丰满的人妻完整版| 亚洲不卡免费看| 国产 一区精品| 亚洲成人久久爱视频| 999久久久精品免费观看国产| 99久久无色码亚洲精品果冻| 亚洲,欧美,日韩| a级毛片免费高清观看在线播放| 亚洲在线观看片| 国产91精品成人一区二区三区| 内地一区二区视频在线| 国产精品av视频在线免费观看| 日本黄色片子视频| 国产精品无大码| 三级毛片av免费| 人妻夜夜爽99麻豆av| 美女cb高潮喷水在线观看| 免费av不卡在线播放| 99国产精品一区二区蜜桃av| 熟妇人妻久久中文字幕3abv| 观看美女的网站| 看黄色毛片网站| 亚洲av成人av| 啦啦啦观看免费观看视频高清| 国产精品国产三级国产av玫瑰| 久久久久久久久久久丰满 | 欧美丝袜亚洲另类 | 精品午夜福利视频在线观看一区| 无遮挡黄片免费观看| 亚洲人成伊人成综合网2020| 欧美+亚洲+日韩+国产| 别揉我奶头~嗯~啊~动态视频| 国产午夜福利久久久久久| 亚洲va在线va天堂va国产| 免费av不卡在线播放| 啪啪无遮挡十八禁网站| 日日夜夜操网爽| 精品人妻1区二区| 男女视频在线观看网站免费| 久久久久久久亚洲中文字幕| 夜夜看夜夜爽夜夜摸| 我要搜黄色片| 亚洲国产精品久久男人天堂| 免费无遮挡裸体视频| 久久久成人免费电影| 国产亚洲av嫩草精品影院| 色综合婷婷激情| 3wmmmm亚洲av在线观看| 欧美成人一区二区免费高清观看| 亚洲在线自拍视频| 深夜a级毛片| 亚洲四区av| 欧美日韩国产亚洲二区| 国产91精品成人一区二区三区| 国产69精品久久久久777片| 亚洲中文字幕日韩| 日本五十路高清| 久久人人精品亚洲av| 女生性感内裤真人,穿戴方法视频| 亚洲精品456在线播放app | 长腿黑丝高跟| 久久久国产成人免费| 免费一级毛片在线播放高清视频| 人妻夜夜爽99麻豆av| 偷拍熟女少妇极品色| 久久久久久久久久久丰满 | 偷拍熟女少妇极品色| 久久人妻av系列| 国产三级中文精品| 久久久久国内视频| 免费观看在线日韩| 久9热在线精品视频| 12—13女人毛片做爰片一| 午夜精品久久久久久毛片777| 成人av一区二区三区在线看| 中文字幕精品亚洲无线码一区| 午夜福利高清视频| 在线免费观看不下载黄p国产 | 99热这里只有精品一区| 久久精品夜夜夜夜夜久久蜜豆| 女的被弄到高潮叫床怎么办 | 亚洲在线自拍视频| 亚洲国产欧美人成| 亚洲午夜理论影院| 一级毛片久久久久久久久女| 欧美人与善性xxx| 日本爱情动作片www.在线观看 | 国产精品av视频在线免费观看| 国产久久久一区二区三区| 日韩欧美一区二区三区在线观看| 99久久成人亚洲精品观看| 91麻豆精品激情在线观看国产| 真实男女啪啪啪动态图| 精品久久国产蜜桃| 亚洲性久久影院| 日韩欧美免费精品| 国产白丝娇喘喷水9色精品| 看黄色毛片网站| 亚洲av免费在线观看| 级片在线观看| 国产欧美日韩精品亚洲av| 啦啦啦观看免费观看视频高清| 国产一区二区在线av高清观看| 中文字幕av在线有码专区| 极品教师在线免费播放| 色综合色国产| 夜夜爽天天搞| 99视频精品全部免费 在线| 久久九九热精品免费| 日韩欧美 国产精品| 热99re8久久精品国产| 亚洲精品一区av在线观看| 啦啦啦啦在线视频资源| 一区福利在线观看| 国产在线精品亚洲第一网站| 国产精品一区二区三区四区久久| 直男gayav资源| 自拍偷自拍亚洲精品老妇| 97热精品久久久久久| av在线亚洲专区| 亚洲av成人av| 无人区码免费观看不卡| 国产白丝娇喘喷水9色精品| 亚洲无线在线观看| 日韩欧美国产在线观看| 国产真实伦视频高清在线观看 | 欧美不卡视频在线免费观看| 天堂√8在线中文| 蜜桃久久精品国产亚洲av| 1000部很黄的大片| 日本 欧美在线| 成人永久免费在线观看视频| 色综合站精品国产| 国内精品久久久久精免费| 久久久久久伊人网av| 校园春色视频在线观看| 久久欧美精品欧美久久欧美| 国产亚洲av嫩草精品影院| 国产精品国产高清国产av| 床上黄色一级片| 久久精品国产亚洲av天美| 日韩欧美精品v在线| 男人的好看免费观看在线视频| 91狼人影院| 亚洲熟妇中文字幕五十中出| 亚洲美女搞黄在线观看 | 亚洲精品在线观看二区| 毛片女人毛片| 国产高清视频在线观看网站| 美女被艹到高潮喷水动态| 最近视频中文字幕2019在线8| 欧美日本视频| 嫩草影院入口| 91久久精品电影网| 成人鲁丝片一二三区免费| 草草在线视频免费看| 天堂网av新在线| 亚洲av日韩精品久久久久久密| 国产精品99久久久久久久久| 午夜老司机福利剧场| 91久久精品电影网| 蜜桃亚洲精品一区二区三区| 男女做爰动态图高潮gif福利片| 精品一区二区三区av网在线观看| 亚洲精品国产成人久久av| 人妻制服诱惑在线中文字幕| 日韩欧美精品免费久久| 一进一出抽搐gif免费好疼| 欧美丝袜亚洲另类 | 亚洲三级黄色毛片| 欧美日韩乱码在线| 国产精品亚洲一级av第二区| 午夜激情欧美在线| 久久精品夜夜夜夜夜久久蜜豆| 99热这里只有是精品50| or卡值多少钱| 国产精品1区2区在线观看.| 精品一区二区三区视频在线| 成人三级黄色视频| 男女那种视频在线观看| a级毛片a级免费在线| 伊人久久精品亚洲午夜| 国产亚洲精品久久久com| 婷婷精品国产亚洲av在线| 99热这里只有精品一区| 床上黄色一级片| 欧美绝顶高潮抽搐喷水| 禁无遮挡网站| 人人妻人人澡欧美一区二区| 精品人妻一区二区三区麻豆 | av视频在线观看入口| 久久香蕉精品热| 日韩 亚洲 欧美在线| 精品人妻视频免费看| 中文在线观看免费www的网站| 亚洲av日韩精品久久久久久密| 看免费成人av毛片| 日韩av在线大香蕉| 日本黄大片高清| 干丝袜人妻中文字幕| 亚洲成人中文字幕在线播放| 亚洲精品乱码久久久v下载方式| 少妇的逼好多水| 国产精品99久久久久久久久| 嫁个100分男人电影在线观看| 亚洲专区中文字幕在线| 九九爱精品视频在线观看| 99在线人妻在线中文字幕| 免费看光身美女| 日韩欧美精品免费久久| av中文乱码字幕在线| 亚洲精品乱码久久久v下载方式| 亚洲精品粉嫩美女一区| 婷婷亚洲欧美| 可以在线观看的亚洲视频| 一a级毛片在线观看| 十八禁国产超污无遮挡网站| 超碰av人人做人人爽久久| 在线a可以看的网站| 中文字幕精品亚洲无线码一区| 国产主播在线观看一区二区| 国产精品电影一区二区三区| 99国产精品一区二区蜜桃av| 国产精品综合久久久久久久免费| 极品教师在线视频| 哪里可以看免费的av片| 婷婷亚洲欧美| 亚洲人与动物交配视频| 久久99热这里只有精品18| 免费一级毛片在线播放高清视频| 99久久无色码亚洲精品果冻| 午夜福利高清视频| aaaaa片日本免费| 亚洲精品在线观看二区| 国产视频内射| 精品久久久久久,| 精品日产1卡2卡| 欧美日韩精品成人综合77777| 内地一区二区视频在线| 久久久久久久久大av| 日本黄色片子视频| 国产三级在线视频| 99久国产av精品| av国产免费在线观看| 国产v大片淫在线免费观看| 亚洲欧美日韩无卡精品| 婷婷丁香在线五月| 国产主播在线观看一区二区| 国产久久久一区二区三区| 我的女老师完整版在线观看| 亚洲av成人精品一区久久| 国产精品三级大全| 日韩一区二区视频免费看| 舔av片在线| 欧美激情久久久久久爽电影| videossex国产| 日本黄色视频三级网站网址| 成年女人毛片免费观看观看9| 热99在线观看视频| 真实男女啪啪啪动态图| 精品午夜福利在线看| 国产在线男女| 嫩草影院精品99| av在线亚洲专区| 一区二区三区四区激情视频 | 在线免费十八禁| 日韩一本色道免费dvd| 美女高潮的动态| 精品国产三级普通话版| 中文在线观看免费www的网站| 久久人人爽人人爽人人片va| 亚洲精华国产精华液的使用体验 | 2021天堂中文幕一二区在线观| 国产色爽女视频免费观看| 日本a在线网址| 久久热精品热| 一本精品99久久精品77| 精品免费久久久久久久清纯| 久久热精品热| 乱码一卡2卡4卡精品| 日本爱情动作片www.在线观看 | 日韩强制内射视频| 在线观看免费视频日本深夜| 亚洲精品456在线播放app | 日韩精品中文字幕看吧| 美女 人体艺术 gogo| 在线免费观看的www视频| 成人高潮视频无遮挡免费网站| 国产真实乱freesex| 国产伦精品一区二区三区视频9| 日日摸夜夜添夜夜添av毛片 | 日韩欧美 国产精品| 久久精品国产亚洲av天美| 深爱激情五月婷婷| 身体一侧抽搐| 欧美国产日韩亚洲一区| 俄罗斯特黄特色一大片| 99久久久亚洲精品蜜臀av| 99久久成人亚洲精品观看| 在线观看美女被高潮喷水网站| 91久久精品电影网| 午夜久久久久精精品| 日日干狠狠操夜夜爽| 久久欧美精品欧美久久欧美| 亚洲在线观看片| 精品久久久久久久末码| 国产 一区精品| 少妇的逼水好多| 日本欧美国产在线视频| 男女做爰动态图高潮gif福利片| 伦精品一区二区三区|