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ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 74-81

Adverse effects of perinatal protein restriction on regulators of lipid metabolism and hepatic function in offspring of sprague-dawley rats


Department of Physiology, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Submission25-Dec-2020
Date of Decision10-Jan-2021
Date of Acceptance12-Jan-2021
Date of Web Publication10-Aug-2021

Correspondence Address:
Dr. Igbayilola Yusuff Dimeji
Department of Physiology, College of Medicine, University of Lagos, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njecp.njecp_49_20

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  Abstract 


Background: Adequate evidence suggests that a poor in utero environment produced by early-life dietary disturbance may predispose offspring to chronic diseases in later life. It remains to be defined which of the windows of early exposure due to perinatal protein restriction (PPR) (gestation, lactation, and/or both) is more detrimental to the regulators of lipid metabolism and hepatic functions of the offspring in later life. Hence, the current study investigated the role of PPR on regulators of lipid metabolism and hepatic functions in adult offspring. Materials and Methods: Twenty-four pregnant Sprague-Dawley rats were used and fed either a control (CONT) diet containing 20% protein or protein-restricted (PR) diet with 8% protein. The dams were given PR diet up to parturition (in utero group, in utero protein restriction [IUPR]), or from birth to postnatal day (PND) 21 (lactation group, lactational protein restriction [LPR]) or for a period covering both (combined protein restriction [CPR]). On PND 126, triglycerides (TG), cholesterol (CHOL), low density lipoprotein (LDL), and high density lipoprotein (HDL) were determined and Castelli indices I and II were calculated. Hepatic lipase (HL) and lipoprotein lipase (LPL), aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), and serum albumin were also assessed. Results: There was a significant decrease (P < 0.01) in HDL with a significant increase (P < 0.01) in TG and LDL in IUPR and CPR offspring compared with CONT. The Castelli index I was significantly increased (P < 0.01) in all PR offspring with a significant increase (P < 0.01) in Castelli index II in LPR offspring compared with CONT. HL and LPL activities reduced significantly (P < 0.01) in all PR offspring. PPR produced a significant reduction (P < 0.01) in AST with a significant elevation in ALT in all PR, while ALT heightened significantly (P < 0.01) in CPR offspring. A significant decrease (P < 0.01) was observed in albumin level in CPR offspring compared with CONT. Conclusion: In conclusion, it is evidenced that PPR at critical periods of early-life exposure blunted remarkably the actions of HL and LPL which consequently led to impairment of lipid metabolism and hepatic dysfunction.

Keywords: Intrauterine, lipase, lipid, perinatal, protein, Sprague-Dawley


How to cite this article:
Dimeji IY, Olufemi MA, Bolanle O I. Adverse effects of perinatal protein restriction on regulators of lipid metabolism and hepatic function in offspring of sprague-dawley rats. Niger J Exp Clin Biosci 2021;9:74-81

How to cite this URL:
Dimeji IY, Olufemi MA, Bolanle O I. Adverse effects of perinatal protein restriction on regulators of lipid metabolism and hepatic function in offspring of sprague-dawley rats. Niger J Exp Clin Biosci [serial online] 2021 [cited 2021 Dec 4];9:74-81. Available from: https://www.njecbonline.org/text.asp?2021/9/2/74/323672




  Introduction Top


Prenatal and postnatal dietary influence, combined with changes in lifestyle in adult life, can result in an increased risk of chronic diseases.[1] The notion that the intrauterine environment may influence the development of the fetus is not novel However, the concept that fetal development predate on-adult diseases has arisen relatively recently and led to a revival of interest in the influence of the in utero environment on the fetus and neonate.[2] Previous studies have reported that an offspring stands a high chance of survival if the nutritional exposure during pregnancy is the same as postnatal exposure.[3]

These changes in nutritional factors play a role in fetal programming including deficiency of nutrients, energy restriction, and inadequate food intake during pregnancy or postnatal[3] and this has been shown to result in fetal intrauterine growth restriction. There is substantial evidence supporting the role of fetal and early postnatal nutrition in the development of homeostatic mechanisms of the fetus and infant. These effects can also influence the risk of diabetes, obesity, dyslipidemia, and other components of metabolic syndrome in later life.[4],[5] The role of early-life nutritional exposure to later life health has been referred to as fetal programming, which is defined as the process whereby a stimulus during a critical period of early-life development results in long-term physiological effects.[6],[7]

Excess intakes of energy,[2] total fat and saturated fatty acids, protein and vitamins, folic acid, and vitamin result in programming of adverse metabolic effect in the offspring. An important example is the deficiency of protein diet which has been shown to result in into metabolic disorders both in human and several experimental studies.[8],[9] Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism, and immune function.[10] Physicochemical properties, amino acid composition, and bioactive peptides encrypted in amino acid sequences of proteins contribute to the physiological functions of proteins.[10]

Lipids are essential for energy homeostasis, reproductive and organ physiology, and numerous aspects of cellular biology. They are also associated with many pathological processes, such as obesity, diabetes, heart disease, and inflammation. To meet the different demands from a variety of tissues, the human body has evolved a sophisticated lipoprotein transport system to deliver cholesterol and fatty acids to the periphery exemplified by the metabolic syndrome, or syndrome X, which refers to patients who are insulin-resistant (hyperinsulinemic), dyslipidemic (elevated triglyceride [TG] and decreased high-density lipoprotein [HDL]-cholesterol levels [CHOLs]), and at high risk for developing coronary artery disease (CAD).[11]

The liver is a major metabolic organ and plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually, the accumulation of lipid droplets results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in β-oxidation, very low-density lipoprotein (LDL) secretion, and pathways involved in the synthesis of fatty acids.[12] Previous studies on perinatal protein restriction (PPR) (4% protein) during the last third of gestation showed that the offspring exhibited elevated LDL and reduced HDL with increased Castelli indices I and II.[9] Hyperlipidemia in rats exposed to protein restriction during gestation was reported.[8],[13]

Epidemiological and experimental studies demonstrated that the consequences of inadequate protein nutrition in utero may extend to adulthood and could lead to metabolic disorders. The mismatch between the metabolic programming acquired during fetal life and postnatal development that the individual will confront in later life would be at the beginning of a high predisposition to develop dysfunctions such as dyslipidemia and obesity. It remains to be defined which of the windows of early exposure due to PPR (gestation, lactation, and/or both) is more detrimental to regulators of lipid metabolism and hepatic functions as it affects the offspring in later life. In this study, we investigated the offspring of Sprague-Dawley rats exposed to PPR during different windows of exposure, namely in utero, lactational and combined to access the:

  1. Impact of PPR on indices of lipid profile such as CHOL, TG, HDL, and LDL
  2. Effect of PPR on regulators of lipid metabolism such as hepatic lipase (HL) and lipoprotein lipase (LPL)
  3. Effects of PPR on markers of hepatic functions such as aspartate aminotransferase (AST), alkaline aminotransferase (ALT), alkaline phosphatase (ALP), and albumin
  4. Whether the effects are dependent on the windows of exposure.



  Materials and Methods Top


Experimental animals and ethical approval

Twenty-four virgin female and 12 male Sprague-Dawley rats were used for this investigation. Sprague-Dawley rats were kept in a room with controlled temperature (25°C ± 1°C) and with an artificial dark-light cycle 12 h light/dark cycle. Ethical approval was given by the Institutional Animal Care and Use Research Ethics Committee to conduct the study with reference number CMUL/HREC/07/19/564.

Diet

The protein-restricted (PR) diet was 8% protein and the control (CONT) diet was 20% protein diet Chisari et al. Female Sprague-Dawley rats were mated overnight with confirmed male breeders and a smear from vagina which was washed with normal saline solution (NaCl, 0.9%w/v) was taken to determine the presence of spermatozoa.[8] After pelletizing the animal feeds, they were analyzed for moisture, protein, fat, ash, fiber, and nitrogen-free extract by the methods of AOAC, as highlighted in [Table 1].[14]
Table 1: Composition of experimental diets (k/kg)

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Mating and grouping

Female Sprague-Dawley rats were mated overnight with confirmed male breeders and a smear from vaginal which was washed with normal saline solution (NaCl, 0.9%w/v) was taken to determine the presence of spermatozoa.[8] Pregnant rats were individually housed in plastic cages and allocated at random to one of four groups which was fed with either a 20% protein (CONT diet) or 8% protein (PR) diet. Food and water were made available to all animals. In utero protein restriction (IUPR) group was fed with PR diet only during gestation; lactational protein restriction (LPR) group received PR diet only during lactation; and the third group combined protein restriction (CPR) received PR diet throughout gestation and lactation. CONT group was fed with a normal rat diet throughout the experiment. Reproductive performance of these dams in the various groups are shown below [Table 2]. Litters were reduced to 8–10 pups on postnatal day (PND) 1 (birth, day 0). They were weaned on PND 21 and housed in groups of three or four male rats per cage. All male pups were transitioned to CONT diet until the end of the experiment (PND 120–128). For consistency, only male offspring were used for the study because early-life programming is known to occur in a sexually dimorphic manner[15] which was outside the focus of this study.
Table 2: Reproductive performance in dams fed with control and protein-restricted diets

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Collection of blood sample

The rats were lightly anesthetized with isoflurane (5% for 2 min), and the eyelid is pulled back to proptose the eye for retro-orbital bleeding. Blood samples collected were allowed to clot for 1 h at 4°C and centrifuged at 3000 rpm for 10 min. Serum samples obtained were kept at −20°C until analyses.[16] This procedure was performed on PND 126.

Tissue isolation

On PND 128, the rats were sacrificed using decapitation. The animals were dissected; the liver tissue was removed and washed in an ice cold and rinsed with 1.15% KCl, blotted after which all the tissues were weighed.

Blood and liver homogenate lipids

Serum and liver homogenate lipid levels of TG, CHOL, LDL, and HDL after treatment were determined by an automatic biochemistry analyzer (Mindray BS-120, Chema Diagnostica, Italy) using diagnostic kits for each, purchased from BioSystems® (S. A Costa Brava of Barcelona, Spain).

Quantification of Castelli index

To determine the Castelli indices I and II, the following calculations were used:

Castelli index I = Cholesterol/HDL cholesterol

Castelli index II = LDL cholesterol/HDL cholesterol.[9],[17]

Hepatic lipase and lipoprotein lipase

HL and LPL activities were determined in liver and adipose tissue homogenates, respectively. The assay system (final volume 1 ml) contained 0.1 ml of glyceride emulsion, 0.2 ml of serum albumin, and 0.6 ml of 0.1 M phosphate buffer (pH 7.4). 0.1 ml of enzyme approximately 200 pg of lipase protein dissolved in glass-distilled water. Incubation lasted for 60 min at 37oC in a shaking water bath. Lipase activities were assayed measuring the increase in absorbance at 546 nm bath.[18],[19]

Liver functions

Albumin, ALP, ALT, and AST were determined using both serum and liver homogenate samples by an automated analyzer (Mindray BS-120, Chema Diagnostica, Italy).

Statistical analysis

All results were presented as the mean and standard error of mean. Statistical analyses were conducted using GraphPad Prism Software (GraphPad, Inc., La Jolla, CA, USA). Data analyses were performed by one-way analysis of variance with post hoc Tukey's multiple comparison test. Statistical significance was set at P < 0.01.


  Results Top


Lipid profile (serum)

A significant decrease (P < 0.01) was observed in serum CHOL in IUPR (1.73 ± 0.02) compared with CONT; however, there was no statistically significant difference (P > 0.01) in LPR (1.85 ± 0.02) and CPR (1.78 ± 0.04). There was a statistically significant increase (P < 0.01) in serum TG levels in IUPR (0.83 ± 0.03) and CPR (0.87 ± 0.03) with no statistically significant difference (P > 0.01) in LPR (0.65 ± 0.03) compared with CONT (0.67 ± 0.03). There was no statistically significant difference (P > 0.01) in serum HDL levels in IUPR (0.97 ± 0.02), LPR (0.93 ± 0.03), and CPR (0.93 ± 0.03) compared with CONT. There was no statistically significant difference (P > 0.01) in serum HDL levels in LPR (0.93 ± 0.03) and CPR (0.93 ± 0.03) groups compared with IUPR (0.97 ± 0.02), and no significant difference (P > 0.01) was observed in CPR (0.93 ± 0.03) compared with LPR (0.93 ± 0.03). There was a significant increase (P < 0.01) in serum LDL levels in IUPR (0.90 ± 0.01) and CPR (0.92 ± 0.02) with no statistically significant difference (P > 0.05) in LPR (0.58 ± 0.02) compared with CONT [Table 3].
Table 3: Cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein levels in control and offspring exposed to perinatal protein restriction

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Castelli indices

A significant increase (P < 0.01) was observed in Castelli index I in IUPR, LPR, and CPR compared with CONT. Furthermore, Castelli index I displayed a significant increase and decrease (P < 0.01) in LPR and CPR offspring, respectively, compared with IUPR, while CPR offspring was significantly reduced (P < 0.01) compared with LPR. There was no statistically significant difference (P > 0.01) in Castelli index II in IUPR and CPR, while the index was significantly heightened (P < 0.01) in LPR compared with CONT [Figure 1].
Figure 1: Castelli indices I and II in control and offspring exposed to perinatal protein restriction. Values represent mean ± standard error of mean; Significant levels (#P < 0.01 vs. CONT, aP < 0.01 vs. in utero protein restriction, 1P < 0.01 vs. lactation protein restriction). Control; in utero protein restriction; lactation protein restriction; combined protein restriction

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Lipid profile (liver homogenate)

[Table 4] shows no statistically significant difference (P > 0.01) in the level of CHOL in IUPR (2.26 ± 0.02) and LPR (2.26 ± 0.07) with a significant decrease (P < 0.01) in CPR (2.06 ± 0.04) compared with CONT (2.26 ± 0.02). PPR also displayed a significant decrease (P < 0.01) in CHOL level in CPR offspring (2.06 ± 0.04) compared with IUPR (2.26 ± 0.07) and CPR (2.26 ± 0.07). TG levels in IUPR (0.66 ± 0.04) and CPR (0.96 ± 0.02) were significantly increased compared with CONT (0.52 ± 0.04) with no statistically significant difference (P > 0.01) in LPR (0.62 ± 0.02). However, PPR showed a significant increase (P < 0.01) in TG level in CPR (0.96 ± 0.02) compared with IUPR (2.26 ± 0.07) and LPR (2.26 ± 0.07). There was no statistically significant difference (P > 0.01) in HDL level in liver homogenate of IUPR (1.24 ± 0.02), while the level significantly reduced (P < 0.01) in LPR (1.10 ± 0.04) and CPR (1.04 ± 0.04) compared with CONT (1.34 ± 0.04). HDL level significantly decreased (P < 0.01) in LPR (1.10 ± 0.04) and CPR (1.04 ± 0.04) compared with IUPR (1.24 ± 0.02).
Table 4: Cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein levels in control and offspring exposed to perinatal protein restriction

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A significant increase (P < 0.01) was observed in LDL in IUPR (0.84 ± 0.02) and CPR (0.85 ± 0.03) compared with CONT (0.68 ± 0.03) and no statistically significant difference (P > 0.01) in LPR (0.66 ± 0.02) though a reduction was observed compared with CONT (0.68 ± 0.03). LDL significantly heightened in CPR (0.85 ± 0.03) compared with LPR (0.66 ± 0.02).

Hepatic lipase and lipoprotein lipase

A significant increase (P < 0.01) was observed in HL activity in IUPR, LPR, and CPR compared with CONT. In addition, HL activity heightened significantly (P < 0.01) in LPR and CPR compared with IUPR. LPL activity in IUPR, LPR, and CPR significantly decreased (P < 0.01) compared with CONT [Figure 2].
Figure 2: Hepatic lipase and lipoprotein lipase in control and offspring exposed to perinatal protein restriction. Values represent mean ± standard error of mean; Significant levels (#P < 0.01 vs. control, aP < 0.01 vs. in utero protein restriction). Control; in utero protein restriction; lactation protein restriction; combined protein restriction

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Hepatic functions (serum)

[Table 5] shows a significant decrease (P < 0.01) in serum ALT (AST) levels in IUPR (54.80 ± 0.37), LPR (57.60 ± 0.51), and CPR (48.20 ± 0.37) compared with CONT (59.80 ± 0.58). AST significantly increased and decreased, respectively, in LPR and CPR (48.20 ± 0.37) compared with IUPR (54.80 ± 0.37). In addition, PPR produced a significant decrease (P < 0.01) in AST level in CPR (48.20 ± 0.37) compared with LPR (57.60 ± 0.51). There was a significant decrease (P < 0.01) in serum ALT levels in IUPR (20.80 ± 0.58), LPR, and CPR (18.80 ± 0.73) groups compared with CONT (59.80 ± 0.58). PPR also produced a significant decrease (P < 0.01) in ALT level CPR (18.80 ± 0.73) compared with LPR (23.80 ± 1.82). Despite increase, there was no statistically significant difference (P > 0.01) in serum ALP levels in IUPR (20.20 ± 0.20) and LPR (19.40 ± 0.51), while the level in CPR (28.0 ± 0.51) significantly increased (P < 0.01) compared with CONT (19.20 ± 0.37). However, PPR produced a significant increase (P < 0.01) in the ALP level of CPR compared with IUPR (20.20 ± 0.20) and LPR (19.40 ± 0.51).
Table 5: Aspartate aminotransferase, alkaline aminotransferase, and alkaline phosphatase levels in control and offspring exposed to perinatal protein restriction

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[Table 5] also shows no statistically significant difference (P > 0.01) in serum albumin levels in IUPR (40.20 ± 0.37) and LPR (38.80 ± 0.37) but significantly decreased (P < 0.01) in CPR (37.80 ± 0.37) compared with CONT (39.40 ± 0.40) and IUPR (40.20 ± 0.37).

Hepatic functions (liver homogenate)

We examined the effect of PPR on hepatic functions from liver homogenate. [Table 6] shows a significant decrease (P < 0.01) in AST levels in IUPR (76.00 ± 0.55), LPR (72.00 ± 0.55), and CPR (48.20 ± 0.37) compared with CONT (61.00 ± 0.63). Furthermore, the current study showed a significant decrease in AST level in LPR (72.00 ± 0.55) and CPR (48.20 ± 0.37) compared with IUPR (76.00 ± 0.55) and a significant decrease in CPR (48.20 ± 0.37) compared with LPR (72.00 ± 0.55). There was a significant increase (P < 0.01) in ALT levels in IUPR (116.20 ± 0.58), LPR (126.80 ± 1.46), and CPR (122.20 ± 0.58) compared with CONT (112.00 ± 0.71). The result also showed a significant increase (P < 0.01) in ALT levels in LPR (126.80 ± 1.46) and CPR (122.20 ± 0.58) compared with IUPR (116.20 ± 0.58) and a significant decrease in CPR (122.20 ± 0.58) compared with LPR (126.80 ± 1.46). ALP level showed a significant decrease (P < 0.01) in IUPR with no statistically significant difference (P > 0.01) in LPR (9.00 ± 0.01) and CPR (9.00 ± 0.32) despite elevation in ALP levels. However, ALP significantly heightened (P < 0.01) in LPR (9.00 ± 0.01) and CPR (9.00 ± 0.32) compared with IUPR (6.40 ± 0.24).
Table 6: Aspartate aminotransferase, alkaline aminotransferase, and alkaline phosphatase levels in control and offspring exposed to perinatal protein restriction

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  Discussion Top


There has been an upsurge in the prevalence of metabolic disorders such as obesity and dyslipidemia. Prenatal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Epidemiological and experimental studies revealed that maternal diet is a major modifier of the development of homeostatic regulatory systems in the offspring in utero and postnatally. Both protein content and source in maternal diet influence pre- and early postnatal development of the offspring.[10]

PPR did affect lipid metabolism as determined in 4 months old offspring. The current study revealed hypertriglyceridemia, LDL-hypercholesterolemia, and HDL-hypocholesterolemia with a significant increase in TG and LDL and reduction in HDL suggesting impairment of lipid metabolism. Elevated plasma TG levels have been reported as a risk factor for coronary heart disease.[20],[21] Hypertriglyceridemia, LDL-hypercholesterolemia, and HDL-hypocholesterolemia are well-known risk factors for dyslipidemia and development of obesity, a component of metabolic syndrome.[10] Increased serum LDL and decreased serum HDL concentrations are strong risk factors for the development of atherosclerosis.[22] Hyperlipidemia is a heterogeneous group of disorders characterized by the high level of lipids in the bloodstream. It may be caused by disorders of some endocrine glands, kidneys, effects of certain drugs, dietary intake containing a high amount of fat, risky lifestyle, and aging.[20] It is one of the risk factors in the development of atherosclerosis.[23]

Lipids are essential for energy homeostasis, reproductive and organ physiology, and numerous aspects of cellular biology. They are also associated with many pathological processes, such as obesity, diabetes, heart disease, and inflammation. To meet the different demands from a variety of tissues, the human body has evolved a sophisticated lipoprotein transport system to deliver cholesterol and fatty acids to the periphery exemplified by the metabolic syndrome, or syndrome X, which refers to patients who are insulin-resistant (hyperinsulinemic), dyslipidemic (elevated TG and decreased HDL-CHOLs), and at high risk for developing CAD.[11]

Most studies have examined the effect of PPR on lipid levels in young offspring and there are limited data in older offspring. A couple of studies have shown that protein restriction throughout pregnancy and lactation malprogram offspring to impaired lipid metabolism. Male rats exposed to protein restriction during the last third of gestation show elevated LDL,[9] hyperlipidemia in rats exposed to protein restriction during gestation,[8],[12] and elevated level of TG in rats exposed to protein restriction during gestation.[8] These are consistent with the current findings.

A previous study showed that cholesterol dysregulation in offspring whose dams were fed a PR diet (8%) during pregnancy and lactation could cause early program changes through epigenetic mechanisms by histone modification, which repressed the cholesterol 7-hydroxylase promoter.[13] In addition, the high Castelli index in IUPR and CPR offspring suggested a possible increased risk of arteriogenesis risk. However, a high Castelli index has been reported as an important indicator for an increased risk of atherosclerosis development.[9],[14]

Furthermore, the current study is the first study on PPR to understudy the roles of HL and LPL on lipid metabolism. HL is a lipolytic enzyme synthesized mostly by hepatocytes and found localized at the surface of liver sinusoidal capillaries. It can be considered as a lipase of the vascular compartment, together with LPL, with which it shares a number of structural and functional similarities. HL exerts both TG lipase and phospholipase A1 activities and is involved at different steps of lipoprotein metabolism.[15] The results showed downregulation in HL and LPL activities in all PR offspring which is suggestive of impairment of lipid metabolism. Previous studies have demonstrated that the liver contains lipases (glycerol-ester hydrolase) capable of hydrolyzing glycerides.[18]

It has been reported that elevation of the LPL activity results in reducing TG level in the blood and reduction of the plasma TG level and elevation of the plasma HDL cholesterol by activation of LPL may be useful for the prevention of dyslipidemia. Hypertriglyceridemia and HDL-hypocholesterolemia are well-known risk factors for atherosclerosis.[24] Reduced function of LPL has been found to result in dyslipidemia, obesity, insulin resistance, and atherosclerosis.[24] It is therefore evident from the current findings that PPR induces dysfunction of lipid metabolism in offspring of Sprague-Dawley rats.

The liver is a major metabolic organ and plays a key role in lipid metabolism. Depending on species, it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually, the accumulation of lipid droplets results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in β-oxidation, very LDL secretion, and pathways involved in the synthesis of fatty acids.[12]

A significant downregulation was observed in all the liver enzymes in PR offspring with the exception of serum ALP level and ALT levels in the liver homogenate which upregulated in CPR and all PR offspring. Imbalance in the activities of the liver enzymes may be suggestive of hepatic dysfunction.

Albumin is the most important plasma protein produced by the liver and is a useful indicator of liver function. The current study showed a reduction in serum albumin levels in CPR offspring. Hypoalbuminemia has been reported to occur due to protein malnutrition.[25] It has been described as an important dietary protein requirement, the lack of them in the diet, partial or chronically determined chronic liver disease with hepatocellular deterioration reported that a low protein diet during pregnancy and lactation induces offspring liver dysfunction. These are consistent with the current findings. Hence, it is evident from the current findings that PPR produces hepatic dysfunction.


  Conclusion Top


In conclusion, the data described in the current study provide evidence that PPR, at critical periods of early life exposure to dietary manipulations malprogram to impairment of lipid metabolism such as dyslipidemia. PPR consequently resulted into liver dysfunction arising from increased levels of the hepatic enzymes. This suggests that in-utero window appears to be the most susceptible window of exposure to perinatal protein diet restriction and disturbance at a critical period of development may compromise health in adulthood.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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