Peter J Havel

Peter J Havel
University of California, Davis | UCD · Departments of Molecular Biosciences and Nutrition

DVM, PhD

About

407
Publications
53,211
Reads
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26,184
Citations
Citations since 2017
85 Research Items
8133 Citations
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201720182019202020212022202302004006008001,0001,2001,400
201720182019202020212022202302004006008001,0001,2001,400
201720182019202020212022202302004006008001,0001,2001,400
Introduction
Dr. Havel is investigating the involvement of endocrine systems in the pathophysiology of obesity, diabetes, and cardiovascular disease. His laboratory is performing highly translational research investigating mechanisms regulating the secretion of pancreatic and gastrointestinal hormones (GLP-1) and the production of the adipocyte hormones (leptin and adiponectin) and the role of endocrine systems in the pathophysiology and pharmacological and surgical prevention and treatment of type-2 diabetes, CVD and NAFLD/NASH. The interactions between endocrine, metabolic, and dietary factors in regulating energy balance, insulin action, and lipid/carbohydrate metabolism is being investigated in humans and UCD-T2DM Rat and high sugar diet-induced rhesus macaque models developed in his laboratory.
Additional affiliations
June 1988 - September 2019
University of California, Davis
Position
  • Professor (Full)
Education
September 1989 - June 1994
University of California, Davis
Field of study
  • Veterinary Medicine
September 1989 - August 1994
University of California, Davis
Field of study
  • Endocrinology

Publications

Publications (407)
Article
Full-text available
Introduction: Studies in humans and animals have found that type 2 diabetes mellitus (T2DM) exaggerates the blood pressure (BP) response to exercise, which increases the risk of adverse cardiovascular events such as heart attack and stroke. T2DM is a chronic disease that, without appropriate management, progresses in severity as individuals grow ol...
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Introduction: The incretin hormone glucagon-like peptide-1 (GLP-1) slows gastric emptying, increases satiety and enhances insulin secretion. GLP-1 receptor agonists, such as liraglutide, are used therapeutically in humans to improve glycaemic control and delay the onset of type 2 diabetes mellitus (T2DM). In UCD-T2DM rats, a model of polygenic obe...
Article
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We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhi...
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The onset of type II diabetes increases the heart’s susceptibility to oxidative damage because of the associated inflammation and diminished antioxidant response. Transcription factor NF-κB initiates inflammation while Nrf2 controls antioxidant defense. Current evidence suggests crosstalk between these transcription factors that may become dysregul...
Article
Studies have shown that pressor responses to muscle contraction and tendon stretch are exaggerated in type 2 diabetes mellitus (T2DM). Low-grade inflammation, which contributes to the underlying pathology of T2DM, involves an increase in pro-inflammatory cytokines. These cytokines are known to play a role in exaggerating the pressor response during...
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Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 ye...
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Non-alcoholic fatty liver disease (NAFLD) is a common liver pathology that includes steatosis, or non-alcoholic fatty liver (NAFL), and non-alcoholic steatohepatitis (NASH). Without a clear pathophysiological mechanism, it affects Hispanics disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) and inflammatory lipid...
Preprint
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Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies from steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). With no clear mechanism, it affects Hispanics in the U.S. disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) metabolism and downstream inflammatory lipid mediators includin...
Article
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A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay...
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The role of pyruvate dehydrogenase in mediating lipid-induced insulin resistance stands as a central question in the pathogenesis of type 2 diabetes mellitus. Many researchers have invoked the Randle hypothesis to explain the reduced glucose disposal in skeletal muscle by envisioning an elevated acetyl CoA pool arising from increased oxidation of f...
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Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of Califo...
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Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in...
Article
Dysregulation of hepatic glucose production (HGP) and glucose disposal leads to hyperglycemia and type 2 diabetes. Hyperglycemia results from the declining ability of insulin to reduce HGP and increase glucose disposal, as well as inadequate ß-cell compensation for insulin resistance. Hyperglucagonemia resulting from reduced suppression of glucagon...
Article
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Previous studies have indicated that oxytocin (OT) reduces body weight in diet-induced obese (DIO) rodents through reductions in energy intake and increases in energy expenditure. We recently demonstrated that hindbrain [fourth ventricular (4V)] administration of OT evokes weight loss and elevates interscapular brown adipose tissue temperature (TIB...
Article
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Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. The objectives of this study were to examine whether there were (1) sex differences in aortic function and (2) alterations in the relative contribution of endothelium-derived relaxing factors in modulating aortic reactivity in UC Davis Type 2 Di...
Article
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Context Studies in rodents and humans suggest that high fructose corn syrup (HFCS)-sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets. Objective To compare the effects of consuming sucrose-sweetened beverage (-SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans. Design A par...
Article
Full-text available
Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that includes steatosis (NAFL) and nonalcoholic steatohepatitis (NASH). In the U.S., Hispanics (HIS) are afflicted with NAFLD at a higher rate and severity compared to other ethnicities. To date, the mechanisms underlying this disparity have not been elucidated. In this pilot study...
Article
Pancreatic β-cells are crucial regulators of systemic glucose homeostasis, and their dysfunction and loss are a central feature in type 2 diabetes. Interventions that rectify β-cell dysfunction and loss are essential to combat this deadly malady. In the current study, we sought to delineate the role of soluble epoxide hydrolase (sEH) in β-cells und...
Preprint
Full-text available
Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that includes steatosis (NAFL) and nonalcoholic steatohepatitis (NASH). In the U.S., Hispanics (HIS) are afflicted with NAFLD at a higher rate and severity compared to other ethnicities. To date, the mechanisms underlying this disparity have not been elucidated. In this pilot study...
Article
Full-text available
Overconsumption of sugar-sweetened beverages increases risk factors associated with cardiometabolic disease, in part due to hepatic fructose overload. However, it is not clear whether consumption of beverages containing fructose as naturally occurring sugar produces equivalent metabolic dysregulation as beverages containing added sugars. We compare...
Article
Previous studies indicate that oxytocin (OT) administration reduces body weight in high fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these finding...
Article
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Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 yea...
Article
Aims: To investigate the contributions of two factors potentially impairing glucagon response to insulin-induced hypoglycemia (IIH) in insulin-deficient diabetes: 1. loss of paracrine disinhibition by intra-islet insulin, 2. defects in the activation of the autonomic inputs to the islet. Methods: Plasma glucagon responses during hyperinsulinemic...
Article
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There has been little innovation in identifying novel insulin sensitizers. Metformin, developed in the 1920s, is still used first for most Type 2 diabetes patients. Mice with genetic reduction of p52Shc protein have improved insulin sensitivity and glucose tolerance. By high-throughput screening, idebenone was isolated as the first small molecule '...
Article
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Background: Fructose consumption increases risk factors for cardiometabolic disease. It is assumed that the effects of free sugars on risk factors are less potent because they contain less fructose. We compared the effects of consuming fructose, glucose or their combination, high fructose corn syrup (HFCS), on cardiometabolic risk factors. Method...
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Alterations of transition metal levels have been associated with obesity, hepatic steatosis, and metabolic syndrome in humans. Studies in animals indicate an association between dietary sugars and copper metabolism. Our group has conducted a study in which young adults consumed beverages sweetened with glucose, fructose, high fructose corn syrup (H...
Article
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The gut microbiome has the potential to create or modify xenometabolites (i.e., non-host derived metabolites) through de novo synthesis or modification of exogenous and endogenous compounds. While there are isolated examples of xenometabolites influencing host health and disease, wide-scale characterization of these metabolites remain limited. We d...
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Moringa seeds have been used traditionally in the management of type 2 diabetes mellitus (T2DM) and contain potent bioactive isothiocyanates. This study evaluated the efficacy of an isothiocyanate-rich moringa seed extract in delaying the onset of T2DM in UC Davis T2DM rats, a well validated model which closely mimics T2DM in humans. Rats were sepa...
Article
Rodent studies demonstrate that compared with diets sweetened with sucrose, high fructose corn syrup (HFCS) produces greater metabolic dysfunction. However, the effects of sustained consumption of HFCS and sucrose have not been adequately compared in humans. The objective of this study was to compare HFCS-, sucrose-, or aspartame- sweetened beverag...
Article
Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. However, there is insufficient evidence to establish the timeline of the vascular dysfunction in diabetes, specifically in relation to sex. Here, we determined whether mesenteric arterial function is altered in UC Davis Type-2 Diabetes Mellitus...
Article
Atorvastatin is a synthetic statin administered in its active form and used for the treatment of dyslipidemias. In the current study, the effects of atorvastatin were evaluated on plasma lipid profiles and the potential for adverse effects after once daily PO dosing of atorvastatin for 30 days in Hispaniolan Amazon parrots (Amazona ventralis). Sixt...
Article
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Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for therapies for managing cardiovascular disease. Here we investigated the effect of a high-sugar (fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ~30–40% after 1 and 3 months of a high-fructose...
Article
Several studies have shown vascular dysfunction in diabetic rats, however, there is no data on the vascular function of UC Davis type 2 diabetes Mellitus (UCD-T2DM) rats. UCD-T2DM is a novel but validated model of type 2 diabetes (T2D) which more closely resembles the pathophysiology of diabetes in humans. The aim of this study was to determine whe...
Article
Ileal interposition (IT) is a surgical procedure that increases the delivery of incompletely digested nutrients and biliary and pancreatic secretions to the distal intestinal mucosa. Here, we investigated the metabolic impact of this intervention in 2-mo-old prediabetic University of California, Davis type 2 diabetes mellitus rats by assessing live...
Article
Type 2 diabetes mellitus (T2DM) patients have exaggerated sympathetic activity and blood pressure responses to exercise. However, the underlying mechanisms for these responses, as well as how these responses change throughout disease progression, are not completely understood. For this study, we examined the effect of the progression of T2DM on the...
Article
MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (includin...
Article
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ApoCIII and triglyceride (TG)-rich lipoproteins (TRL), particularly, large TG-rich lipoproteins particles, have been described as important mediators of cardiovascular disease (CVD) risk. The effects of sustained consumption of dietary fructose compared with those of sustained glucose consumption on circulating apoCIII and large TRL particles have...
Article
CRP is produced by the liver in response to factors released from macrophages and adipocytes. High circulating CRP concentrations are therefore an indicator of inflammation and/or injury. We examined the effects of dietary fructose on plasma CRP concentrations in a nonhuman primate model of diet-induced metabolic syndrome. Adult male rhesus macaque...
Article
Global sugar consumption is at an all-time high. In previous studies, we and others have demonstrated that, compared with glucose (Gluc), consumption of fructose (Fruc) increases risk factors for cardiovascular disease (CVD), diabetes and metabolic syndrome. However, humans almost exclusively consume Fruc in combination with Gluc. Our aim was to st...
Article
Homozygous loss-of-function ANGPTL3variants are associated with familial combined hypolipidemia, suggesting the dual LPL/EL inhibitor is a promising target for treating atherogenic dyslipidemia. However, nothing is known regarding the dietary regulation of ANGPTL3, including effects of dietary sugar or n-3 fatty acids. We investigated plasma ANGPTL...
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Mouse studies linking adropin, a peptide hormone encoded by the energy homeostasis associated (ENHO) gene, to biological clocks and to glucose and lipid metabolism suggest a potential therapeutic target for managing diseases of metabolism. However, adropin's roles in human metabolism are unclear. In silico expression profiling in a nonhuman primate...
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Significance Lipoprotein lipase (LPL) plays a central role in plasma lipid metabolism, hydrolyzing the triglycerides in lipoproteins and releasing fatty acid nutrients for vital tissues. LPL is synthesized by adipocytes and myocytes and secreted into the interstitial spaces, whereupon it is captured by an endothelial cell protein, GPIHBP1, and tran...
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Dyslipidemia and insulin resistance are significant adverse outcomes of consuming high-sugar diets. Conversely, dietary fish oil reduces plasma lipids. Diet-induced dyslipidemia in a rhesus model better approximates the pathophysiology of human metabolic syndrome than rodent models. Here we investigated relationships between metabolic parameters an...
Article
The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male UCD-T2DM rats before the onset of diabetes (pre-diabetic PD, n=...
Article
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Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric cont...
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Aims/hypothesis: In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increas...
Article
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Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages (SSB) increases risk factors involved in the development of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD). Our previous study demonstrated that when compared to aspartame (Asp), two weeks of high-...
Article
More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe u...