About

Yves R Boisclair is a Professor of Integrative Physiology in the Department of Animal Science at Cornell University. His professional activities are centered around understanding the role of hormones in regulating mammalian metabolism. His research involves many animal models, including mice, sheep, and cattle, each offering unique opportunities and metabolic challenges. The overall goal of his research program is to understand the regulation of metabolism, growth, and development by hormones, pursuing this at molecular, cellular, and organismal levels in the context of problems relevant to animal agriculture and medicine. His work specifically focuses on the role of the growth hormone-IGF system in regulating growth, productive function, and metabolism, as well as the roles of adipokines and hepatokines such as leptin, adiponectin, and fibroblast growth factor-21 in coordinating adaptive metabolism during demanding physiological states like pregnancy and lactation.

Research topics

• Biology
• Chemistry
• Biochemistry
• Internal medicine
• Cell biology
• Medicine
• Endocrinology

Selected publications

• 123 Fibroblast growth factor 21 (FGF21) improves insulin action in obese sheep.

  Journal of Animal Science · 2025-10-01

  articleOpen accessSenior author

  Abstract Insulin resistance (IR) is a fundamental mechanism regulating nutrient partitioning in ruminants. IR promotes the diversion of maternal nutrients toward fetal growth in late pregnant ewes but can become excessive and increase susceptibility to pregnancy toxemia in obese ewes. The novel hormone fibroblast growth factor 21 (FGF21) has been shown to act as an insulin-sensitizing hormone in rodents and non-human primates, but its effects in ruminants experiencing IR remain unclear. This study aimed to assess whether FGF21 can improve insulin action in ewes experiencing insulin resistance as a consequence of obesity. To create groups differing in fatness, twelve non-pregnant, non-lactating Finn × Dorset ewes were assigned to either a restricted or unrestricted feeding regimen for 48 weeks. Initial body weight (55.0±1.3 kg) and subcutaneous backfat thickness (4.9±0.2 mm) were similar across groups. Over the next 48 weeks, the unrestricted group became obese, gaining significantly more body weight (55 vs. 9 kg; P < 0.01) and subcutaneous backfat thickness (7 vs. 0 mm; P < 0.01) than the lean restricted group. Ewes from each group were then used in a single reversal design with treatment and intervening periods of 7 days each; both groups were fed at 1.1 times their individual maintenance energy requirements during the experimental periods. Treatments were daily subcutaneous injections of excipient or human FGF21 (12.5 mg/kg of metabolic body weight). Obese ewes experienced marked insulin resistance, with 3.3-fold higher plasma insulin and 1.9-fold higher free fatty acids (P < 0.01), along with impaired glucose disposal during glucose and insulin tolerance tests (P ≤ 0.05). FGF21 treatment reduced plasma glucose irrespective of fatness (P = 0.02). FGF21 treatment progressively decreased plasma insulin in obese ewes (FGF21 × Day,P = 0.02) but had no effect in lean ewes. FGF21 reduced the insulin response area in both lean and obese ewes during glucose tolerance tests (P < 0.01) and increased insulin-dependent glucose disposal irrespective of fatness (P = 0.04) during insulin tolerance tests. FGF21 effects were associated with a progressive increase in plasma concentration of the insulin-sensitizing hormone adiponectin in lean ewes but not in obese ewes (FGF21 × Fatness × Day, P = 0.05). These findings confirm the ability of FGF21 to alleviate insulin resistance in ruminants and show that the insulin-sensitizing effects of FGF21 do not require increased plasma adiponectin. Funding Sources: The CNPq award 201955/2017-2 to ACRS and NIFA-USDA award 7005434 to YRB.

  PublisherOA PDFDOI

• Insulin-sensitizing effects of fibroblast growth factor-21 in underfed sheep

  Journal of Animal Science · 2025-01-01

  articleSenior author

  Reversal of insulin resistance by fibroblast growth factor-21(FGF21) in rodent and non-human primate models of obesity and in well-fed (WF) sheep was associated with increased production of the insulin-sensitizing hormone adiponectin. In contrast, FGF21 therapy failed to increase plasma adiponectin and improve insulin action in energy-deficient ruminants facing metabolically demanding states such as early lactation dairy cows. The goal of the study was to test the hypothesis that FGF21 is unable to improve insulin action in energy-deficient ruminants as a consequence of its failure to increase plasma adiponectin. Non-pregnant, non-lactating ewes were treated for 12 d with FGF21 or excipient when WF (2-fold of maintenance energy requirement, n = 4) or underfed (UF; 0.5-fold of maintenance energy requirement, n = 4). Plasma variables were measured as indices of insulin action (glucose, insulin, and adiponectin), lipolysis (fatty acids), and ketogenesis (β-hydroxybutyrate) on days 1, 4, 7, 10, and 12 of treatment. The effect of treatments on insulin action was assessed by measuring glucose disposal during insulin tolerance tests on day 10 and glucose tolerance tests on day 11. Quantitative RT-PCR was used to measure expression of genes mediating FGF21 effects in adipose tissue. Underfed ewes lost weight (energy balance, EB, P < 0.01) and had reduced plasma glucose (EB, P = 0.04) and insulin (EB × Day, P = 0.01), confirming negative EB. In UF ewes, FGF21 retained the ability to reduce plasma glucose (FGF21, P = 0.02) but not plasma insulin. FGF21 improved insulin action in both WF and UF ewes during glucose (insulin response area; FGF21, P = 0.02) and insulin tolerance tests (FGF21, P = 0.04) and did so in the absence of increased plasma adiponectin in UF ewes. Underfeeding reduced adipose tissue expression of the FGF21 co-receptor β-Klotho (EB, P < 0.01) and attenuated FGF21 stimulation of the FGF-responsive genes SPRY4 (EB × FGF21, P = 0.07) and DUSP4 (EB × FGF21, P = 0.02). FGF21 failed to increase adiponectin mRNA expression at both feeding levels. FGF21 had no effect on plasma fatty acids but reduced plasma β-hydroxybutyrate in UF ewes (EB × FGF21, P = 0.02). These data show that energy insufficiency alone does not prevent FGF21 improvement of insulin action in ruminants and that increased adiponectin production is not necessary for FGF21 insulin-sensitizing effects.

  PublisherDOI

• Persisting Insulin-Sensitizing Effects of Fibroblast Growth Factor-21 (FGF21) in Underfed Sheep

  Current Developments in Nutrition · 2025-05-01

  articleOpen accessSenior author

  Objectives: Reversal of insulin resistance by FGF21 in rodent and non-human primate models of obesity is associated with increased production of the insulin-sensitizing hormone adiponectin. In contrast, FGF21 therapy failed to increase plasma adiponectin and improve insulin action in energy-deficient ruminants facing metabolically demanding states such as early lactation. The study tested the hypothesis that FGF21 is unable to improve insulin action in energy-deficient ruminants as a consequence of its failure to increase plasma adiponectin.

  PublisherOA PDFDOI

• Effect of metabolic disturbances on the plasma concentration and hepatic expression of the appetite-reducing hormone growth differentiation factor 15 (GDF15) in dairy cows

  Journal of Dairy Science · 2025-10-21

  articleOpen accessSenior author

  Early-lactating dairy cows are vulnerable to metabolic dysfunctions and diseases and the consequent negative effects of these disturbances on appetite. The exaggerated response of early-lactating cows to metabolic disturbances is illustrated by their response to a hyperinsulinemic-euglycemic clamp (HEC) performed over a 48-h period. Initiation of HEC on d 7 of early lactation (EL) reduced feed intake by 33% but had no effect when performed in late pregnancy (LP, 31 d prepartum). We asked whether growth differentiation factor 15 (GDF15), a novel hormone inhibiting feed intake via activation of neuronal centers, could explain the effect of HEC on appetite in EL. This focus was prompted by increased GDF15 production in primates and rodents experiencing metabolic stressors. In plasma samples collected immediately before and after a 48-h period of HEC in EL and LP, HEC increased plasma GDF15 exclusively in EL, and this increase was positively associated with the reduction in feed intake. The major site of GDF15 production in EL was identified as liver on the basis of 7.7- to 87-fold higher expression than adipose tissue or muscle and increased hepatic GDF15 mRNA abundance during HEC. The HEC stimulated hepatic expression of the GDF15 transcriptional activators ATF4 and CHOP across physiological states and expression of the indicator of amino acid deficiency ASNS in EL but not LP. We next asked whether plasma GDF15 is also regulated by a subset of metabolic disturbances prevailing in EL cows (elevated plasma fatty acids, excessive liver triglyceride, and ketosis). The effect of increased plasma fatty acids was evaluated by i.v. infusion of a lipid emulsion (intralipid) in nonpregnant, nonlactating cows in the absence or presence of glucagon treatment. Intralipid caused a progressive rise in plasma GDF15; this stimulatory effect was increased in the presence of glucagon, resulting in a 2.4-fold increase over control after 13 h of infusion. Positive effects of intralipid were associated with increased hepatic expression of GDF15 and its transcriptional activators ATF4 and sXBP1; presence of glucagon increased GDF15 mRNA further but had no additional effect on ATF4 or sXBP1. Indices of GDF15 production were examined in healthy cows segregated on d 7 of lactation as having low (<5.2%) and high (>11.5%) liver triglyceride; neither plasma GDF15 nor hepatic GDF15 mRNA differed between the 2 groups. Finally, plasma GDF15 was measured in early-lactating dairy cows remaining healthy or diagnosed with clinical ketosis. Plasma GDF15 was 1.8-fold higher in ketotic than healthy cows. Overall, these data show upregulation of GDF15 production by a subset of metabolic factors and raise the possibility that GDF15 could contribute to the lower appetitive drive of early-lactating cows experiencing metabolic disturbances.

  PublisherDOI

• Potential involvement of peroxisome proliferator-activated receptors in the inhibition of mammary lipid synthesis during diet-induced milk fat depression

  Journal of Dairy Science · 2024-11-08

  articleOpen access

  The objective of this study was to evaluate the possible role of the peroxisome proliferator-activated receptors (PPAR: PPAR-α, PPAR-β/δ, and PPAR-γ) in diet and CLA-induced milk fat depression (MFD) in dairy cows. We hypothesized that the expression of PPAR, which regulate lipid metabolism and bind to PUFA, could be modulated by biohydrogenation intermediates that induce MFD, thereby interfering with milk fat synthesis. First, tissue profiling revealed that PPAR-α and PPAR-β/δ had low expression in mammary tissue compared with the liver. A comparison of lactating and nonlactating tissue from the same cows showed that expression of all 3 PPAR isoforms did increase during lactation. Mammary expression of the PPAR family during MFD was then observed in 9 mid-lactation cows in a 3 × 3 Latin square design with MFD induced by a 3-d intravenous infusion of trans-10,cis-12 CLA or feeding a high-oil and low-forage diet. The expression of all 3 PPAR isoforms remained largely unaltered during CLA and diet-induced MFD, except for an increase in PPAR-α target genes CPT1A and ACADVL that are involved in β-oxidation. The interaction of PPAR-γ chemical agonist troglitazone and antagonist T0070907 and CLA was then investigated in bovine mammary epithelial cells. The activation and inhibition of PPAR-γ did not overcome trans-10,cis-12 CLA inhibition of lipogenesis despite the agonist stimulating PPAR-γ expression. Furthermore, PPAR-γ activation did not modify the expression of lipogenic genes. Overall, the results fail to support a functional role of the PPAR family in the inhibition of lipogenesis during MFD in dairy cows.

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• International Symposium on Ruminant Physiology: Endocrine adaptations to demanding physiological states in ruminants

  Journal of Dairy Science · 2024-12-07 · 1 citations

  reviewOpen access1st authorCorresponding

  Highly productive ruminants rely on hormonally driven adaptations to prioritize the use of limiting nutrients during the demanding phases of the pregnancy-lactation cycle. Glucose, the predominant oxidative fuel of fetal life and the absolute precursor of mammary lactose synthesis, illustrates the need and benefit of such adaptations. Endocrine mechanisms such as insulin resistance or hypoinsulinemia favor the diversion of maternal glucose to the placenta or mammary gland where uptake is independent of insulin. Research in dairy cows in the 1980s and 1990s identified growth hormone as a peripherally acting signal opposing the effects of insulin. The following decades have seen the discovery of a new generation of signals secreted almost exclusively by adipose tissue, skeletal muscle, or liver, dynamically regulated by metabolic challenges, and engaged in cross-organ communication. The understanding of these signals in the coordination of metabolism in ruminants has been limited by the availability of assays to measure their circulating concentrations and materials to perform functional studies. Nevertheless, emerging data point to their importance during demanding physiological states in ruminants, including early lactation in dairy cows and late pregnancy in sheep. Examples include modulation of insulin action by liver-derived fibroblast growth factor 21 (FGF21) and regulation of energy allocation among tissues by the action of the adipose-derived hormone leptin via its ability to control the hypothalamic-pituitary-thyroid axis. Recent studies investigating the regulation and action of FGF21 and leptin in dairy cows and sheep will be used to illustrate the potential of recently discovered signals to coordinate metabolism during physiologically demanding states such as early lactation.

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• Inflammatory tone in liver and adipose tissue in dairy cows experiencing a healthy transition from late pregnancy to early lactation

  Journal of Dairy Science · 2023-08-23 · 4 citations

  articleOpen accessSenior authorCorresponding

  The transition from late pregnancy (LP) to early lactation (EL) in dairy cows is characterized by a major reorganization of the metabolic activities of liver and adipose tissue in support of milk synthesis. This reorganization has been attributed in large part to variation in the plasma concentration and actions of growth hormone, insulin, and other metabolic hormones. A role for the immune system has also been suggested by a near-universal rise in circulating levels of liver-derived acute-phase proteins (APP) in early lactating cows. However, less attention has been devoted to the possibility that resident macrophages of liver and adipose tissue adopt a proinflammatory state (referred herein as inflammatory tone) in parallel with the rise in plasma APP. We addressed this question by measuring the expression of genes expressed predominantly in the resident macrophage population of liver and adipose tissue and indicative of a proinflammatory (tumor necrosis factor α, IL-6, IL-12, resistin, and cluster of differentiation 80 [CD80]) or anti-inflammatory state (IL-10 and chitinase-3-like protein 1 [CHI3L1]). In a first group of cows, none of these inflammatory gene markers were regulated in liver between LP on d -29 (relative to parturition) and on d 8 of EL despite 1.7 to 5.6-fold upregulation in the expression of the APP (haptoglobin, serum amyloid α, and orosomucoid 1). In a second group of healthy cows, expression of the inflammatory gene markers did not differ between livers with low (<5.3%) or high (>11.5%) triglyceride content on d 7 of EL. In adipose tissue, a modest increase in inflammatory tone was suggested between LP and EL by increased CD80 expression and decreased CHI3L1 expression in EL. To assess the possibility that inflammatory tone would be more prominent if assayed in a cell compartment enriched with macrophages, adipose tissue was obtained in LP on d -28 and in EL on d +10 from cows experiencing a healthy transition period and fractionated into its adipocyte and stromal vascular cell (SVC) compartments. Expression of inflammatory gene markers was higher in SVC than adipocytes but remained unregulated in SVC between LP and EL. Overall, these results suggest little change in the inflammatory tone of resident macrophages in liver and adipose tissue of healthy transition dairy cows and do not support a role for the local immune system in the reorganization of metabolism in these tissues at the onset of lactation.

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• Effects of the central melanocortin system on feed intake, metabolic hormones and insulin action in the sheep

  Journal of Animal Science · 2023-01-01 · 4 citations

  articleOpen accessSenior author

  Voluntary feed intake is insufficient to meet the nutrient demands associated with late pregnancy in prolific ewes and early lactation in high-yielding dairy cows. Under these conditions, peripheral signals such as growth hormone and ceramides trigger adaptations aimed at preserving metabolic well-being. Recent work in rodents has shown that the central nervous system-melanocortin (CNS-MC) system, consisting of alpha-melanocyte-stimulating hormone (α-MSH) and agouti-related peptide (AGRP) acting respectively as agonist and antagonist on central MC receptors, contributes to the regulation of some of the same adaptations. To assess the effects of the CNC-MC on peripheral adaptations in ruminants, ewes were implanted with an intracerebroventricular cannula in the third ventricle and infused over days with artificial cerebrospinal fluid (aCSF), the α-MSH analog melanotan-I (MTI), or AGRP. Infusion of MTI at 0.03 nmol/h reduced intake, expressed as a fold of maintenance energy requirement (M), from 1.8 to 1.1 M (P < 0.0001), whereas AGRP at 0.3 nmol/h increased intake from 1.8 to 2.0 M (P < 0.01); these doses were used in all subsequent experiments. To assess the effect of MTI on plasma variables, sheep were fed ad libitum and infused with aCSF or MTI or pair-fed to MTI-treated sheep and infused with aCSF (aCSFPF). Feed intake of the MTI and aCSFPF groups was 40% lower than the aCSF group (P < 0.0001). MTI increased plasma triiodothyronine and thyroxine in an intake-independent manner (P < 0.05 or less) but was devoid of effects on plasma glucose, insulin, and cortisol. None of these variables were altered by AGRP infusion in sheep fed at a fixed intake of 1.6 M. To assess the effect of CNS-MC activation on insulin action, ewes were infused with aCSF or MTI over the last 3 d of a 14-d period when energy intake was limited to 0.3 M and studied under basal conditions and during hyperinsulinemic-euglycemic clamps. MTI had no effect on plasma glucose, plasma insulin, or glucose entry rate under basal conditions but blunted the ability of insulin to inhibit endogenous glucose production during hyperinsulinemic-euglycemic clamps (P < 0.0001). Finally, MTI tended to reduce plasma leptin in sheep fed at 0.3 M (P < 0.08), and this effect became significant at 0.6 M (P < 0.05); MTI had no effect on plasma adiponectin irrespective of feeding level. These data suggest a role for the CNC-MC in regulating metabolic efficiency and peripheral insulin action.

  PublisherOA PDFDOI

• Fibroblast growth factor-21 improves insulin action in nonlactating ewes

  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · 2022-01-12 · 7 citations

  articleOpen accessSenior authorCorresponding

  During metabolically demanding physiological states, ruminants and other mammals coordinate nutrient use among tissues by varying the set point of insulin action. This set point is regulated in part by metabolic hormones with some antagonizing (e.g., growth hormone and TNFα) and others potentiating (e.g., adiponectin) insulin action. Fibroblast growth factor-21 (FGF21) was recently identified as a sensitizing hormone in rodent and primate models of defective insulin action. FGF21 administration, however, failed to improve insulin action in dairy cows during the naturally occurring insulin resistance of lactation, raising the possibility that ruminants as a class of animals or lactation as a physiological state are unresponsive to FGF21. To start addressing this question, we asked whether FGF21 could improve insulin action in nonlactating ewes. Gene expression studies showed that the ovine FGF21 system resembles that of other species, with liver as the major site of FGF21 expression and adipose tissue as a target tissue based on high expression of the FGF21 receptor complex and activation of p44/42 extracellular signal-regulated kinase (ERK1/2) following exogenous FGF21 administration. FGF21 treatment for 13 days reduced plasma glucose and insulin over the entire treatment period and improved glucose disposal during a glucose tolerance test. FGF21 increased plasma adiponectin by day 3 of treatment but had no effect on the plasma concentrations of total, C16:0-, or C18:0-ceramide. Overall, these data confirm that the insulin-sensitizing effects of FGF21 are conserved in ruminants and raise the possibility that lactation is an FGF21-resistant state.

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• Dietary Fat Does Not Overcome <i>trans</i>‐10, <i>cis</i>‐12 Conjugated Linoleic Acid Inhibition of Milk Fat Synthesis in Lactating mice

  Lipids · 2020-02-24 · 6 citations

  article

  Trans-10, cis-12 conjugated linoleic acid (CLA) is a potent inhibitor of milk fat synthesis in the cow and similarly reduces milk fat in rodents. The objective of this study was to determine whether dietary fat can overcome CLA inhibition of milk fat concentration in lactating mice. Wild type C57Bl/6J mice (n = 31) were fed semipurified diets containing either low fat (LF; 4% fat) or high fat (HF; 23.6% fat) starting 4-6 days postpartum. Dietary fat was increased by inclusion of high oleic sunflower oil. After 2 days on the experimental diets, lactating dams were orally dosed with either water (control) or trans-10, cis-12 CLA (20 mg/day) for 5 days. CLA treatment decreased pup growth similarly in both HF and LF diets. Milk fat percent was increased over 16% by the HF diet and decreased over 12% by CLA, but there was no interaction of dietary fat and CLA. Both CLA and the HF diet reduced the proportion of short- and medium-chain fatty acids that originate from de novo synthesis, and there was no interaction of diet and CLA. CLA had no effect on the percent of preformed fatty acids, but the HF diet increased their abundance. Dietary fat and CLA both modified mammary expression of lipogenic enzymes and regulators, but no interactions were observed. In conclusion, CLA reduced milk fat concentration and litter growth, but these effects were not overcome by increased dietary fat from high oleic sunflower oil. CLA inhibition of milk fat in the mammary gland is not substrate dependent, and the mechanism is independent from dietary supply of oleic acid.

  PublisherDOI

Recent grants

• NIH Grant R01DK051624

  NIH · $2.1M · 2009

Frequent coauthors

• Sarah L. Giesy

  Cornell University

  27 shared

• Guck T. Ooi

  26 shared

• Dale E. Bauman

  University of Vermont

  15 shared

• Richard Ehrhardt

  Michigan State University

  15 shared

• K.J. Harvatine

  Cornell University

  14 shared

• Kelley R. Hurst

  New York State Department of Health

  13 shared

• A. W. Bell

  Eli Lilly (United States)

  12 shared

• Iori Ueki

  Cornell University

  12 shared