1. bookVolume 22 (2022): Issue 2 (April 2022)
Journal Details
First Published
25 Nov 2011
Publication timeframe
4 times per year
access type Open Access

Prenatal programming of the small intestine in piglets: the effect of supplementation with 3-hydroxy-3-methylbutyric acid (HMB) in pregnant sows on the structure of jejunum of their offspring

Published Online: 12 May 2022
Volume & Issue: Volume 22 (2022) - Issue 2 (April 2022)
Page range: 613 - 623
Received: 16 Aug 2021
Accepted: 17 Sep 2021
Journal Details
First Published
25 Nov 2011
Publication timeframe
4 times per year

When discussing the scale of the occurrence of diseases of the digestive system in farm animals, particularly pigs in the weaning period, it may be beneficial to study physiological and nutritional factors that could potentially affect the growth, development, and modelling of the structure and function of the digestive tract. Taking into account the reports on the beneficial effects of ß-hydroxy-ß-methylbutyrate (HMB) administration in the prenatal period on the development of various systems it was assumed that the HMB supplementation to pregnant sows can influence intestinal development in the offspring during weaning. Thus, the present experiment was conducted to evaluate the effect of HMB treatment of pregnant sows on jejunum development in offspring at weaning. From 70th day until the 90th day of gestation, sows received either a basal diet (n = 12) or the same diet supplemented with HMB (n = 12) at the dose of 0.2 g/kg of body weight/day. HMB given during prenatal time reduced the thickness of the longitudinal muscle; the apoptotic cell index in epithelium also significantly decreased after the HMB supplementation. Vasoactive intestinal (poly)peptide (VIP) expression in submucosal ganglia significantly increases in prenatally HMB treated piglets. The same strong reaction was observed with the expression of occludin, claudin-3, E-cadherin, and leptin in the jejunal epithelium. The obtained results indicate that the administration of HMB to pregnant sows significantly influenced the expression of VIP, leptin and some proteins of the intestinal barrier of their offspring less influencing the basal morphology.


Arciszewski M.B., Nowakowski Z., Wasowicz K., Całka J. (2009). Expression of vasoactive intestinal polypeptide, substance P and neuropeptide Y in jejunal enteric nerves is altered in rabbits suffering from long term Trichinella spiralis infection: an immunohistochemical study. Vet. Med., 54: 589597.Search in Google Scholar

Bertram C.E., Hanson M.A. (2002). Prenatal programming of postnatal endocrine responses by glucocorticoids. Reproduction, 124: 459467.Search in Google Scholar

Bik W. (2007). Vasoactive intestinal peptide-immunomodulatory factor and its role in respiratory diseases (in Polish). Post. Nauk Med., 10: 408413.Search in Google Scholar

Blicharski T., Tomaszewska E., Dobrowolski P., Hułas-Stasiak M., Muszyński S. (2017). A metabolite of leucine (β-hydroxy-β-methylbutyrate) given to sows during pregnancy alters bone development of their newborn offspring by hormonal modulation. PLoS One, 12: e0179693.Search in Google Scholar

Czech A., Grela R.E., Kiesz M., Kłys S. (2020). Biochemical and haematological blood parameters of sows and piglets fed a diet with a dried fermented rapeseed meal. Ann. Anim. Sci., 20: 535–550.Search in Google Scholar

Delgado M., Pozo D., Ganea D. (2004). The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol. Rev., 56: 249290.Search in Google Scholar

Dobrowolski P., Muszyński S., Donaldson J., Jakubczak A., Żmuda A., Taszkun I., Rycerz K., Mielnik-Błaszczak M., Kuc D., Tomaszewska E. (2021). The effects of prenatal supplementation with β-hydroxy-β-methylbutyrate and/or alpha-ketoglutaric acid on the development and maturation of mink intestines are dependent on the number of pregnancies and the sex of the offspring. Animals, 11: 1468.Search in Google Scholar

Duan Y., Li F., Song B., Zheng C., Zhong Y., Xu K., Kong X., Yin Y., Wang W., Shu G. (2019). β-hydroxy-β-methyl butyrate, but not α-ketoisocaproate and excess leucine, stimulates skeletal muscle protein metabolism in growing pigs fed low protein diets. J. Funct. Foods, 52: 34–42.Search in Google Scholar

El Karim I.A., Linden G.J., Orr D.F., Lundy F.T. (2008). Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. J. Neuroimmunol., 200: 1116.Search in Google Scholar

Flummer C., Theil P.K. (2012). Effect of β-hydroxy β-methyl butyrate supplementation of sows in late gestation and lactation on sow production of colostrum and milk and piglet performance. J. Anim. Sci., 90: 372–374.Search in Google Scholar

Francis D.H. (1999). Colibacillosis in pigs and its diagnosis. Swine Health Prod., 7: 241244.Search in Google Scholar

Friedman J. (2014). 20 years of leptin: leptin at 20: an overview. J. Endocrinol., 223: T1T8.Search in Google Scholar

Gonzalez-Rey E., Delgado M. (2005). Role of vasoactive intestinal peptide in inflammation and autoimmunity. Curr. Opin. Investig. Drugs., 6: 11161123.Search in Google Scholar

Grela E.R., Skomiał J. (2015). Nutritional recommendations and nutritional value of feed for pigs, 2nd ed. Institute of Physiology and Animal Nutrition of Polish Academy of Science, Jabłonna, Poland, pp. 195.Search in Google Scholar

Groschwitz K.R., Hogan S.P. (2009). Intestinal barrier function: molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol., 124: 320.Search in Google Scholar

Hales C.N., Barker D.J., Clark P.M., Cox L.J., Fall C., Osmond C., Winter P.D. (1991). Fetal and infant growth and impaired glucose tolerance at age 64. Br. Med. J., 303: 10191022.Search in Google Scholar

Hao Y., Jackson J.R., Wang Y., Edens N., Pereira S.L., Alway S.E. (2011). β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 301: R701R715.Search in Google Scholar

Hułas-Stasiak M., Jakubowicz-Gil J., Dobrowolski P., Grzesiak M., Muszyński S., Świątkiewicz M., Tomaszewska E. (2020). Regulation of folliculogenesis by growth factors in piglet ovary exposed prenatally to β-hydroxy-β-methylbutyrate (HMB). Ann. Anim. Sci., 20: 899–917.Search in Google Scholar

Lis I., Bogdański P., Karolkiewicz J. (2014). The effect of β-hydroxy-β-methylbutyrate (HMB) on muscle protein metabolism. Farm Współ., 7: 3241.Search in Google Scholar

Luppi A. (2017). Swine enteric colibacillosis: diagnosis, therapy and antimicrobial resistance. Porc. Health Manag., 3: 16.Search in Google Scholar

Matthews S.G. (2001). Antenatal glucocorticoids and the development brain: mechanisms of action. Semin Neonatol., 6: 309317.Search in Google Scholar

Milart P., Paluszkiewicz P., Dobrowolski P., Tomaszewska E., Smolińska K., Dębińska I., Gaweł K., Walczak K., Bednarski J., Turska M., Raban M., Kocki T., Turski W.A. (2019). Kynurenic acid as the neglected ingredient of commercial baby formulas. Sci. Rep., 9: 6108.Search in Google Scholar

Mou Q., Yang H-S., Yin Y-L., Huang P-F. (2019). Amino acids influencing intestinal development and health of the piglets. Animals, 9: 302.Search in Google Scholar

Nissen S., Abumrad N.N. (1997). Nutritional role of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB). J. Nutr. Biochem., 8: 300311.Search in Google Scholar

Nissen S., Faidley T.D., Zimmerman D.R., Izard R., Fisher C.T. (1994). Colostral milk fat percentage and pig performance are enhanced by feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate to sows. J. Anim. Sci., 72: 2331–2337.Search in Google Scholar

Nissen S., Sharp R.L., Panton L., Vukovich M., Trappe S., Fuller J.C. Jr. (2000). Beta-hydroxy-methylbutyrate (HMB) supplementation in humans is safe and decrease cardiovascular risk factors. J. Nutr., 130: 19371945.Search in Google Scholar

Nowak P., Zaworska-Zakrzewska A., Frankiewicz A., Kasprowicz-Potocka M. (2021). The effects and mechanisms of acids on the health of piglets and weaners – a review. Ann. Anim. Sci., 21: 433–455.Search in Google Scholar

Park H.K., Ahima R.S. (2014). Leptin signaling. F1000Prime Rep., 6: 73.Search in Google Scholar

Pearson P.Y., O’Connor D.M., Schwartz M.Z. (2001). Novel effect of leptin on small intestine adaptation. J. Surg. Res., 97: 192–195.Search in Google Scholar

Rudyk H., Tomaszewska E., Arciszewski M.B., Muszyński S., Tomczyk-Warunek A., Dobrowolski P., Donaldson J., Brezvyn O., Kotsyumbas I. (2020). Histomorphometrical changes in intestine structure and innervation following experimental fumonisins intoxication in male Wistar rats. Pol. J. Vet. Sci., 23: 7788.Search in Google Scholar

Said S.I. (1991). Vasoactive intestinal polypeptide: biologic role in health and disease. Trends Endocrinol Metab., 2: 107–112.Search in Google Scholar

Schneider C.A., Rasband W.S., Eliceiri K.W. (2012). NIH Image to ImageJ: 25 years of image analysis. Nat. Methods, 9: 671–675.Search in Google Scholar

So K-W., Ng P-C. (2005). Treatment and prevention of neonatal osteopenia. Curr. Pediatr., 15: 106–113.Search in Google Scholar

Suvarna S.K., Layton C., Bancroft J.D. (2013). Bancroft’s theory and practice of histological techniques, 7th ed. Churchill Livingstone, New York, NY, USA.Search in Google Scholar

Świetlicka I., Muszyński S., Tomaszewska E., Dobrowolski P., Kwaśniewska A., Świetlicki M., Skic A., Gołacki K. (2016). Prenatally administered HMB modifies the enamel surface roughness in spiny mice offspring: An atomic force microscopy study. Arch. Oral Biol., 70: 2431.Search in Google Scholar

Tatara M.R., Śliwa E., Krupski W. (2007). Prenatal programming of skeletal development in the offspring: effects of maternal treatment with β-hydroxy-β-methylbutyrate (HMB) on femur properties in pigs at slaughter age. Bone, 40: 1615–1622.Search in Google Scholar

Tomaszewska E., Dobrowolski P., Puzio I., Prost Ł., Kurlak P., Sawczuk P., Badzian B., Hułas-Stasiak M., Kostro K. (2014). Acrylamide-induced prenatal programming intestine structure in guinea pig. J. Physiol. Pharmacol., 65: 107–115.Search in Google Scholar

Tomaszewska E., Dobrowolski P., Świetlicka I., Muszyński S., Kostro K., Jakubczak A., Taszkun I., Żmuda A., Rycerz, K., Blicharski T., Jaworska-Adamu J. (2018). Effects of maternal treatment with β-hydroxy-β-metylbutyrate and 2-oxoglutaric acid on femur development in offspring of minks of the standard dark brown type. J. Anim. Physiol. Anim. Nutr., 102: e299–e308.Search in Google Scholar

Tomaszewska E., Muszyński S., Dobrowolski P., Wiącek D., Tomczyk-Warunek A., Świetlicka I., Pierzynowski G.P. (2019). Maternal HMB treatment affects bone and hyaline cartilage development in their weaned piglets via the leptin/osteoprotegerin system. J. Anim. Physiol. Anim. Nutr., 103: 626–643.Search in Google Scholar

Tomaszewska E., Dobrowolski P., Puzio I., Donaldson J., Muszyński S. (2020). Acrylamide-induced prenatal programming of bone structure in mammal model. Ann. Anim. Sci., 20: 1257–1287.Search in Google Scholar

Tomaszewska E., Burmańczuk N., Dobrowolski P., Świątkiewicz M., Donaldson J., Burmańczuk A., Mielnik-Błaszczak M., Kuc D., Milewski S., Muszyński S. (2021). The protective role of alpha-ketoglutaric acid on the growth and bone development of experimentally induced perinatal growth-retarded piglets. Animals, 11: 137.Search in Google Scholar

Tomczyk-Warunek A., Blicharski T., Jarecki J., Dobrowolski P., Muszyński S., Tomaszewska E., Rovati L.C. (2021). The effect of maternal HMB supplementation on bone mechanical and geometrical properties, as well as histomorphometry and immunolocalization of VEGF, TIMP2, MMP13, BMP2 in the bone and cartilage tissue of the humerus of their newborn piglets. PloS One, 16: 2 e024–0642.Search in Google Scholar

Vu J.P., Larauche M., Flores M., Luong L., Norris J., Oh S., Liang L.J., Waschek J., Pisegna J.R., Germano P.M. (2015). Regulation of appetite, body composition, and metabolic hormones by vasoactive intestinal polypeptide (VIP). J. Mol. Neurosci., 56: 377–387.Search in Google Scholar

Winzell M.S., Ahrén B. (2007). Role of VIP and PACAP in islet function. Peptides, 28: 1805–1813.Search in Google Scholar

Xiong X., Tan B., Song M., Ji P., Kim K., Yin Y., Liu Y. (2019). Nutritional intervention for the intestinal development and health of weaned pigs. Front. Vet. Sci., 6: 46.Search in Google Scholar

Yavas C., Yavas G., Acar H., Toy H., Yuce D., Akyurek S., Ata O. (2013). Amelioration of radiation-induced acute inflammation and mucosal atrophy by beta-hydroxy-beta-methylbutyrate, L-glutamıne, and L-argınıne: results of an experimental study. Support Care Cancer, 21: 883–888.Search in Google Scholar

Zheng C., Song B., Duan Y., Zhong Y., Yan Z., Zhang S., Li F. (2020). Dietary β-hydroxy-β-methylbutyrate improves intestinal function in weaned piglets after lipopolysaccharide challenge. Nutrition, 78: 110839.Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo