Effects Of Negative Energy Balance Research Articles

Metabolic evaluation of dairy cows submitted to three different strategies to decrease the effects of negative energy balance in early postpartum

In early lactation dairy cattle suffer metabolic alterations caused by negative energy balance, which predisposes to fatty liver and ketosis. The aim of this study was to evaluate the metabolic condition of high yielding dairy cows subjected to three treatments for preventing severe lipomobilization and ketosis in early lactation. Fifty four multiparous Holstein cows yielding >30 L/day were divided into four groups: control (CN= no treatment), glucose precursor (PG= propylene-glycol), hepatic protector (Mp= Mercepton®), and energy supplement with salts of linolenic and linoleic faty acids (Mg-E= Megalac-E®). Treatments were administrated randomly at moment of calving until 8 weeks postpartum. Blood samples were collected on days 1, 7, 14, 21, 28, 35, 42 and 49 postpartum. Body condition score (BCS) was evaluated at the same periods and milk yield was recorded at 2nd, 4th, 5th, 6th, 7th, and 8th weeks of lactation. Concentrations of non-esterified fatty acids (NEFA), albumin, AST, ß-hydroxybutyrate (BHBA), cholesterol, glucose, total protein, urea and triglycerides were analyzed in blood samples. Cut-off points for subclinical ketosis were defined when BHBA >1.4 mmol/L and NEFA >0.7 mmol/L. General occurrence of subclinical ketosis was 24% during the period. An ascendant curve of cholesterol and glucose was observed from the 1st to the 8th week of lactation, while any tendency was observed with BHBA and NEFA, although differences among treatments were detected (p<0.05). BCS decreased from a mean of 3.85 at 1st week to 2.53 at 8th week of lactation (p=0.001). Milk yield was higher in the Mg-E group compared with the other treatment groups (p<0.05) Compared with the CN group, the treatments with Mp and PG did not show significant differences in blood biochemistry and milk yield. Cows receiving PG and Mg-E showed higher values of BHBA and NEFA (P<0.05), indicating accentuated lipomobilization. Supplementation with Mg-E also resulted in significant higher concentrations of cholesterol, BHBA, urea, AST and lower values of glycemia. This performance may be explained by the highest milk yield observed with this treatment. Treatments with PG and Mp did not improve milk yield, compared with control cows, but did not show metabolic evidence of ketosis, fat mobilization or fatty liver. These results suggest that treatment with Mg-E improves milk production but induces a higher negative energy balance leading to moderated lipomobilization and ketone bodies production, increasing the risk of fatty liver.

Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.

Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: a global approach

In high-yielding dairy cows the liver undergoes extensive physiological and biochemical changes during the early postpartum period in an effort to re-establish metabolic homeostasis and to counteract the adverse effects of negative energy balance (NEB). These adaptations are likely to be mediated by significant alterations in hepatic gene expression. To gain new insights into these events an energy balance model was created using differential feeding and milking regimes to produce two groups of cows with either a mild (MNEB) or severe NEB (SNEB) status. Cows were slaughtered and liver tissues collected on days 6–7 of the first follicular wave postpartum. Using an Affymetrix 23k oligonucleotide bovine array to determine global gene expression in hepatic tissue of these cows, we found a total of 416 genes (189 up- and 227 downregulated) to be altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with widespread changes in gene expression classified into 36 gene networks including those associated with lipid metabolism, connective tissue development and function, cell signaling, cell cycle, and metabolic diseases, the three most significant of which are discussed in detail. SNEB cows displayed reduced expression of transcription activators and signal transducers that regulate the expression of genes and gene networks associated with cell signaling and tissue repair. These alterations are linked with increased expression of abnormal cell cycle and cellular proliferation associated pathways. This study provides new information and insights on the effect of SNEB on gene expression in high-yielding Holstein Friesian dairy cows in the early postpartum period.

Dietary-induced negative energy balance has minimal effects on innate immunity during a Streptococcus uberis mastitis challenge in dairy cows during midlactation

Ten multiparous Holstein cows were used to determine the effects of negative energy balance (NEB) on the immune response to a Streptococcus uberis (strain O140J) mastitis challenge during midlactation. Before the study, milk from all quarters of each cow was bacteriologically negative, with a composite somatic cell count of <200,000 cells/mL. Cows were paired based on parity, days in milk, and milk yield. At approximately 77 d in milk, half the cows (n=5) were feed-restricted to 60% of calculated net energy for lactation requirements to induce NEB. Feed restriction lasted 7 d. Control cows (n=5) were fed the same diet ad libitum (i.e., positive energy balance; PEB). After 5 d, one rear quarter in all cows was inoculated with 5,000 cfu of Strep. uberis. Jugular blood and aseptic quarter milk samples were collected daily until inoculation and every 6h postinoculation for 36h. Blood was analyzed for nonesterified fatty acids, β-hydroxybutyrate, insulin, cortisol, albumin, serum amyloid A (SAA), and haptoglobin (Hp). Periodically throughout the trial period, blood neutrophils were isolated for determination of cell morphology, chemotaxis, and phagocytosis capability in vitro. Quarter milk samples were analyzed for concentrations of SAA, Hp, cytokines (tumor necrosis factor-α, IL-10 and IL-1β), and activity of respiratory burst enzymes (superoxide dismutase and glutathione peroxidase). All cows developed local and systemic signs of mastitis and calculated NEB was similar to that of cows experiencing postpartal NEB. Serum glucose and insulin concentrations increased in both groups after challenge, most likely because of enhanced glycogenolysis and gluconeogenesis; results indicate that immune cell function may be glucose dependent. Serum cortisol concentration was higher in NEB than PEB cows during feed restriction only (before inoculation), and serum albumin concentration was higher in NEB than PEB cows during the infection period. Compared with PEB, cows in NEB had lower SAA concentrations in serum after 5 d of feed restriction but higher SAA concentrations in milk after Strep. uberis challenge. Serum Hp concentration was higher by 36h postchallenge in NEB than in PEB cows. Phagocytic capability of neutrophils was lower in NEB than in PEB cows at 0h of infection but decreased in both PEB and NEB cows through 36h postinfection. Our results indicate that cows subjected to dietary-induced NEB during midlactation had relatively minimal alterations in immune function.

Events of elevated somatic cell counts in high-producing dairy cows are associated with daily body weight loss in early lactation

The objective of this study was to determine associations between body weight (BW) and body condition score (BCS) variables indicating a more severe negative energy balance in early lactation and events of somatic cell counts (SCC) >250,000 cells/mL and SCC >400,000 cells/mL in dairy cows. We studied lactations from 634 primiparous and 1,086 multiparous Israeli Holstein dairy cows originating from 7 commercial dairy farms. Generalized mixed models with a random herd effect were used to quantify the effects of BW and BCS variables in early lactation on events of elevated SCC. Data were analyzed using 2 different approaches. In the first approach, only first events in a lactation were taken into account, whereas in the second approach, all events in a lactation were analyzed and repeated events from the same cow were accounted for. Although no associations were found between the different BW and BCS variables and first events of elevated SCC, associations were present between these variables and events of elevated SCC when all events were analyzed. The cumulative incidence of a lactation with multiple events of SCC >250,000 cells/mL was 8.8 and 27.7% for primiparous and multiparous cows, respectively. The odds of an event of SCC >250,000 cells/mL were 25% greater for cows belonging to the upper quartile in relative BW loss from calving to nadir BW (loss >12.3, 15.0, and 15.7% for first-, second-, and third- parity and greater cows, respectively) compared with cows losing less relative BW. Odds of an event were 44% greater for cows with ketosis when compared with cows without. The cumulative incidence of a lactation with multiple events of SCC >400,000 cells/mL was 4.1 and 14.3% for primiparous and multiparous cows, respectively. The odds of an event of SCC >400,000 cells/mL were 43% greater for cows belonging to the upper quartile in relative BW loss from calving to nadir BW compared with cows losing less relative BW. Odds of an event were 33% greater for cows with ketosis when compared with cows without. Assuming that extreme BW loss and ketosis in early lactation indicate a more severe negative energy balance, our findings support the hypothesis that greater negative energy balance in early lactation predisposes dairy cows to udder inflammation. Considering the fact that many of the events were recurring, we stress the importance of including all events in the analysis and postulate the possibility of long-term detrimental effects of negative energy balance on udder health.

Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity

Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and β-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum. SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-γ; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

Effect of diet-induced energy deficit and body fat reduction on high-sensitive CRP and other inflammatory markers in obese subjects

To dissociate the possible differential effects of negative energy balance and reduction in body fat mass (FM) on inflammatory markers: C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), haptoglobin, transferrin and the adipokines leptin and adiponectin. Thirty-three obese subjects (BMI: 34.0+/-3.1 kg/m(2), age: 43.0+/-10.5 years, mean+/-s.d., 16 men) participated in a 20-week controlled dietary intervention divided into four periods. Weight reduction was induced by an 8-week low energy diet (3.4 MJ d(-1)) (LED-1) followed by a 4-week weight maintenance program (M-1). Subsequently participants underwent an additional 4-week LED (4.2 MJ d(-1)) (LED-2) followed by a final 4-week weight maintenance diet (M-2). Blood samples and anthropometrics were assessed at baseline and after LED-1, M-1, LED-2 and M-2. Body weight was significantly reduced by 13% (13.7+/-4.0 kg, P<0.0001) after LED-1. However, a reduction in high-sensitive CRP (hs-CRP) by 35% (-1.1 (95% CI: -2.5:0.2) mg l(-1), P=0.02) only became apparent after LED-2, which produced an additional weight loss of 2.9 kg compared to baseline, and it was maintained after M-2 (-1.0 (-1.4:0.4) mg l(-1), P=0.02). Also IL-6 was reduced by 21% (-0.6 (-2.4:0.2) ng l(-1), P=0.02) after M-2. The reductions in hs-CRP and IL-6 were both associated with reduction in FM but not body weight. Haptoglobin, transferrin and leptin were significantly reduced after both LED-1 and LED-2, but increased during weight maintenance. Adiponectin was not significantly changed during the intervention. The results suggest that, whereas haptoglobin and transferrin respond more rapidly and are more susceptible to the acute change in energy balance, a reduction in hs-CRP and IL-6 seems to be achieved by a reduction in FM when a new steady state has been established.

Negative energy balance in male and female rangers: effects of 7 d of sustained exercise and food deprivation

A challenging 7-d ranger field exercise (FEX) by cadets in the Norwegian Military Academy provided a venue in which to study the effects of negative energy balance. We quantified total energy expenditure (TEE), food intake, and changes in body composition in male and female cadets. TEE (measured by doubly labeled water), food intake, activity patterns (measured by accelerometry), and body composition (measured by dual-energy X-ray absorptiometry) were measured in 16 cadets (10 men and 6 women aged 21-27 y). The physically active (approximately 23 h/d) and semistarved (0.2-2.2 MJ/d) cadets lost weight (x +/- SD: men, -7.7 +/- 1.1 kg; women, -5.9 +/- 1.1 kg; P < 0.05). Absolute TEE differed by sex (men, 26.6 +/- 2.0 MJ/d; women, 21.9 +/- 2.0 MJ/d; P < 0.05) but body weight-specific TEE did not (men, 343 +/- 26 kJ . kg(-1) . d(-1); women, 354 +/- 18 kJ . kg(-1) . d(-1); NS). Fat-free mass (FFM) loss differed significantly by sex (men, -4.0 +/- 1.2 kg; women, -2.5 +/- 1.1 kg; P < 0.05), but percentage FFM loss did not (men, -6.3 +/- 1.9%; women, -5.6 +/- 2.4%). In contrast, absolute FM loss did not differ significantly by sex (men, -3.45 +/- 0.72 kg; women, -3.42 +/- 0.22 kg), but fat oxidation (men, 5.2 +/- 1.0 mg . min(-1) . kg FFM(-1); women, 7.3 +/- 0.5 mg . min(-1) . kg FFM(-1)) and the relative contribution of FM to TEE (men, 74 +/- 14%; women, 89 +/- 6%) were significantly greater in women than in men (P < 0.05). Female cadets maintained a significantly more fat-predominant fuel metabolism than did male cadets in response to sustained exercise and semistarvation.

The effect of intravenous infusion of glucose on ethanol stability of milk in Holstein dairy cows

The alcohol test is used as the initial classification of milk in dairy farms. It’s used as a measure of the natural pH of milk, which is a critical factor for stabilizing casein micelles in milk serum phase during heating (Barros et al., 2000). In practical conditions the test could be also positive immediately after milking, and this type of milk is rejected by dairy processing industry. An experiment was conducted to evaluate the effects of negative energy balance and low level of blood glucose on incidence of alcohol-positive milk in Holstein high milking cows (Sobhani et al., 2002).

Nutritional effects on resumption of ovarian cyclicity and conception rate in postpartum dairy cows

AbstractIncreased genetic potential for milk production has been associated with a decline in fertility of lactating cows. Following parturition the nutritional requirements increase rapidly with milk production and result in negative energy balance (NEBAL). NEBAL delays the time of first ovulation thereby affecting ovarian cycles before and during the subsequent breeding period The effects of NEBAL on reinitiation of ovulation are manifested through inhibition of LH pulse frequency and low levels of glucose, insulin and IGF-I in blood that collectively restrain oestrogen production by dominant follicles. Upregulation of LH pulses and peripheral IGF-I in association with the NEBAL nadir increases the likelihood that emerging dominant follicles will ovulate. The legacy of NEBAL is reduced fertility after insemination in conjunction with reduced serum progesterone concentrations. Diets high in crude protein support high milk yield, but may be detrimental to reproductive performance. Depending upon protein quantity and composition, serum concentrations of progesterone may be lower and the uterine luminal environment is altered. High protein intake is correlated with plasma urea concentrations that are inversely related to uterine pH and fertility. The direct effects of high dietary protein and plasma urea on embryo quality and development in cattle are inconsistent. In conclusion, the poor fertility of high producing dairy cows reflects the combined effects of a uterine environment that is dependent on progesterone, but has been rendered suboptimal for embryo development by antecedent effects of negative energy balance and may be further compromised by the effects of urea resultingfrom intake of high dietary protein.

Physiological and genetic differences between low and high index dairy cows

AbstractSelection of dairy cattle for increased milk production has decreased some indices of reproductive efficiency. For example, days open are increased by one day for every 100 kg of increased milk yield per lactation. Some of the change in days open can be explained by delayed onset of oestrous cyclicity and lower conception rate to artificial insemination in cows with greater milk production. Despite these negative associations between milk production and reproduction, reproduction in herds of high producing dairy cattle is not necessarily compromised relative to reproduction in herds of low producing dairy cattle. This is because there is a large environmental effect on dairy reproduction. High producing herds generally have better management and better oestrous detection. Therefore, high producing dairy herds may partially overcome the antagonistic relationship between milk production and reproduction. Physiological mechanisms that lead to poorer reproduction in high producing cows are partially defined. Negative energy balance that occurs in high producing dairy cows can be associated with a delay in the initiation of ovarian cycles and the interval to first breeding. Many of the effects of negative energy balance on postpartum reproduction can be explained by decreased serum luteinizing hormone (LH) that is associated with negative energy balance. Serum LH increases as cows move toward positive energy balance and greater LH stimulates growth and ovulation of ovarian follicles. We have initiated studies to address physiological differences in high and low index dairy cows. The reproductive endocrinology of cows from a control line (5,900 kg milk/lactation) and a select line (10,900 kg milk/lactation) of dairy cows at the University of Minnesota was studied over a two-year period. Cows in Year 1 were similar for serum concentrations of LH, follicle stimulating hormone (FSH), and oestradiol (preovulatory period). In both years, serum concentrations of progesterone during luteal phases, however, were decreased in select cows. The Year 2 cows also had a delay in the return to oestrous cyclicity that was associated with reduced LH. The possibility that decreased progesterone causes infertility in dairy cows will require further study. Collectively, these data suggest that changes in blood progesterone concentrations may explain, partially, lower fertility in high index dairy cows.

Effect of acute nutritional restriction on periovulatory oestradiol and IGF-I in beef heifers

Severe negative energy balance (NEB) in the postpartum period of dairy cows may be associated with declining fertility but the mechanisms by which nutrition influences reproduction are complex, poorly understood and confounded by lactation. Hence, both chronic and acute nutritional restriction of beef heifers have been used as models to examine the effects of NEB on ovarian and endocrine responses in the absence of lactation. Plasma IGF-I concentrations gradually decreased until the onset of anoestrus (Stagg et al., 1999) but concentrations may be confounded with stage of the oestrous cycle, especially around ovulation (Mackey et al., 2000). Therefore, the aim of this study was to examine the effect of nutritional restriction on periovulatory oestradiol (E2) and IGF-I concentrations.

Post-Exercise Substrate Utilization after a High Glucose vs. High Fructose Meal During Negative Energy Balance in the Obese

To assess the effects of negative energy balance on the metabolic response of a meal containing either glucose or fructose as the primary source of carbohydrate after exercise in obese individuals in energy balance, or negative energy balance. Fourteen adults with mean body mass index (BMI) 30.3 +/- 1 kg/m2, age 26 +/- 2 years, and weight 93.5 +/- 5.4 kg, adhered to an energy-balanced (EB) or a negative energy-balanced (NEB) diet for 6 days. On Day 7, subjects exercised at 70% VO2peak for 40 minutes then consumed either high glucose (50 g of glucose, HG) or high fructose (50 g of fructose, HF) liquid meal. Substrate utilization was measured by indirect calorimetry for 3 hours. Blood samples were collected before exercise and 0, 30, 60, 120, and 180 minutes after consuming the meal. The HG produced 15.9% greater glycemic (p < 0.05) and 30.9% larger insulinemic (p < 0.05) responses than the HF under both EB and NEB conditions. After the NEB diet, carbohydrate and fat oxidation did not differ for HG and HF. In contrast, carbohydrate oxidation increased 31%, and fat oxidation decreased 39% with HF compared with HG after the EB diet. Thus, HF and HG consumed after exercise produced marked differences in macronutrient oxidation when obese subjects followed an EB diet, but no difference when adhering to a NEB diet. The data suggest that the use of fructose in supplements/meals may provide no additional benefit in terms of substrate utilization during a weight loss program involving diet and exercise.

Energy balance and body condition influence luteal function in holstein heifers

A factorial experiment was conducted to determine influence of energy balance (EB) and body condition (BC) on luteal function in heifers. Heifers with moderate (MBC) or fat (FBC) BC were fed individually to sustain positive EB (PEB) or to cause negative EB (NEB). Intake of feed was measured daily and body weight weekly. Progesterone was quantified daily in serum for 3.5 estrous cycles. On days 9, 10, or 11 after fourth estrus, blood was sampled every 15 min for 12 hr to quantify luteinizing hormone (LH), growth hormone (GH), insulin and non-esterified fatty acids (NEFA). The next day, luteal cells were incubated and proportions of small to large cells were determined. After fourth estrus, area of progesterone profiles in serum for 10 days postestrus was reduced in all heifers relative to MBC-PEB heifers. But, luteal weight from FBC-PEB and MBC-NEB heifers was less than MBC-PEB heifers and FBC-NEB heifers were intermediate. Secretion of progesterone in vitro was increased by LH for PEB but not NEB heifers. MBC-NEB heifers had increased ratios of small to large luteal cells. Independent of BC, NEB decreased concentrations of insulin and increased GH and NEFA. Secretion of progesterone was not associated with LH, GH or insulin, but was correlated negatively with NEFA. We conclude that reduced concentrations of progesterone in serum of FBC-PEB and MBC-NEB heifers is due to impaired luteal development. But, reduced concentrations of progesterone in serum of NEB heifers is due also to reduced basal (MBC) and LH-induced (MBC and FBC) secretion of progesterone by luteal cells. Body condition at onset of NEB may determine when effects of NEB on progesterone are detected.

Energy balance and hypothalamic self-stimulation

The effects of negative energy balance on self-stimulation are a matter of considerable disagreement. This disagreement undoubtedly reflects the inadequacies of the continuous reinforcement self-stimulation procedures used in this type of experimentation. The present experiment uses a new fixed-interval reinforcement shuttle-box procedure which provides indices of reward and stimulation escape that are free from the numerous performance altering effects that confound continuous reinforcement performance. Whereas 24 h of food deprivation had no effect on stimulation initiation or escape rates, 48 h of food deprivation selectively increased initiation rates. The enhancement of reward was seen over virtually the entire anterior-posterior extent of the lateral hypothalamus and occurred irrespective of the occurrence of any stimulus-bound behaviors. Thus negative energy balance appears to selectively increase the excitability of reward-related neurons in the lateral hypothalamus. The self-stimulating rats became clearly hyperphagic, yet their weight gains were not significantly different from those of controls. The self-stimulation must, therefore, have greatly increased energy expenditure. Thus, not only does energy balance affect self-stimulation, but self-stimulation appears to affect energy balance.