Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A

Early lactation in dairy cattle is a period of severe negative energy balance (NEB) characterized by reduced blood glucose and insulin concentrations and elevated blood GH concentrations. The liver is refractory to GH during NEB and this uncoupling of the GH-IGF axis results in diminished plasma concentrations of IGF-I. Our objectives were to examine the effects of insulin administration during the immediate postpartum period on plasma IGF-I and GH concentrations and to examine the hepatic expression of total GH receptors (all GH receptor transcripts), GH receptor 1A (GHR 1A) and IGF-I. In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue. Holstein cows (n=14) were subjected to either a hyperinsulinemic-euglycemic clamp (insulin; INS) or saline infusion (control; CTL) for 96 h starting on day 10 postpartum. Insulin was infused i.v. (1 micro g/kg body weight per h), blood samples were collected hourly, and euglycemia was maintained by infusion of glucose. Insulin concentrations during the infusions were increased 8-fold in INS compared with CTL cows (2.33+/-0.14 vs 0.27+/-0.14 ng/ml (S.E.M.); P<0.001) while blood glucose concentrations were not different between treatments (45.3+/-2.2 vs 42.5+/-2.2 mg/dl; P>0.1). Plasma IGF-I increased continuously during the insulin infusion, and reached the highest concentrations at the end of the clamp, being almost 4-fold higher in INS compared with CTL cows (117+/-4 vs 30+/-4 ng/ml; P<0.001). Hepatic expression of GHR 1A and IGF-I mRNA was low in CTL cows, but was increased 3.6-fold (P<0.05) and 6.3-fold (P<0.001) respectively in INS cows. By contrast, in adipose tissue the changes in gene expression in response to insulin were reversed with decreases in both total GHR and IGF-I mRNA. The expressions of GHR 1A and IGF-I mRNA in liver tissue were correlated in INS (r=0.86; P<0.05), but not CTL cows (r=0.43; P>0.1). Insulin appears to be a key metabolic signal in coupling the GH-IGF axis, thus orchestrating a marked elevation in circulating IGF-I concentrations.

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Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH/IGF-I Axis

International Journal of Molecular Sciences ◽

10.3390/ijms22062827 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2827

Author(s):

Vicente Barrios ◽

Laura M. Frago ◽

Sandra Canelles ◽

Santiago Guerra-Cantera ◽

Eduardo Arilla-Ferreiro ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Negative Energy ◽

Negative Energy Balance ◽

Cytokine Signaling ◽

Mrna Levels ◽

Brown Adipose ◽

Igf I

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.

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Blood free amino acid concentrations in left displacement of the abomasum in dairy cattle with negative energy balance

Japanese Journal of Large Animal Clinics ◽

10.4190/jjlac.2.189 ◽

2011 ◽

Vol 2 (4) ◽

pp. 189-192

Author(s):

M. Hamana ◽

H. Ohtsuka ◽

M. Oikawa ◽

S. Kawamura

Keyword(s):

Amino Acid ◽

Energy Balance ◽

Dairy Cattle ◽

Free Amino Acid ◽

Free Amino ◽

Negative Energy ◽

Negative Energy Balance ◽

Amino Acid Concentrations

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

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200005974 ◽

2001 ◽

Vol 2001 ◽

pp. 215-215 ◽

Cited By ~ 1

Author(s):

D.R. Mackey ◽

A.R.G. Wylie ◽

J.F. Roche ◽

J.M. Sreenan ◽

M.G. Diskin

Keyword(s):

Energy Balance ◽

Dairy Cows ◽

Postpartum Period ◽

Negative Energy ◽

Oestrous Cycle ◽

Negative Energy Balance ◽

Beef Heifers ◽

Igf I ◽

Nutritional Restriction

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.

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Physiological and genetic differences between low and high index dairy cows

BSAP Occasional Publication ◽

10.1017/s0263967x0003370x ◽

2001 ◽

Vol 26 (1) ◽

pp. 223-236 ◽

Cited By ~ 8

Author(s):

M. C. Lucy ◽

B. A. Crooker

Keyword(s):

Energy Balance ◽

Dairy Cattle ◽

Dairy Cows ◽

Milk Production ◽

Negative Energy ◽

High Index ◽

Negative Energy Balance ◽

Positive Energy ◽

Serum Concentrations ◽

Days Open

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.

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Adipose tissue remodeling in late-lactation dairy cows during feed-restriction-induced negative energy balance

Journal of Dairy Science ◽

10.3168/jds.2016-11552 ◽

2016 ◽

Vol 99 (12) ◽

pp. 10009-10021 ◽

Cited By ~ 21

Author(s):

G. Andres Contreras ◽

Kyan Thelen ◽

Sarah E. Schmidt ◽

Clarissa Strieder-Barboza ◽

Courtney L. Preseault ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Dairy Cows ◽

Tissue Remodeling ◽

Negative Energy ◽

Negative Energy Balance ◽

Feed Restriction ◽

Adipose Tissue Remodeling

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

BSAP Occasional Publication ◽

10.1017/s0263967x00033644 ◽

2001 ◽

Vol 26 (1) ◽

pp. 133-145 ◽

Cited By ~ 31

Author(s):

W.R. Butler

Keyword(s):

Energy Balance ◽

Dairy Cows ◽

Milk Production ◽

Dietary Protein ◽

Negative Energy ◽

Negative Energy Balance ◽

Breeding Period ◽

Plasma Urea ◽

Igf I ◽

High Dietary Protein

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.

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