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Article ; Online: Hepatic interoception in health and disease.

Berthoud, Hans-Rudolf / Münzberg, Heike / Morrison, Christopher D / Neuhuber, Winfried L

Autonomic neuroscience : basic & clinical

2024 Volume 253, Page(s) 103174

Abstract: The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. ...

Abstract	The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. A host of neural sensory mechanisms have been proposed, but in contrast to the gut-brain axis, details for both the exact site and molecular signaling steps of their peripheral transduction mechanisms are generally lacking. Similarly, knowledge about function-specific sensory and motor components of both vagal and spinal access pathways to the hepatic parenchyma is missing. Lack of progress largely owes to controversies regarding selectivity of vagal access pathways and extent of hepatocyte innervation. In contrast, there is considerable evidence for glucose sensors in the wall of the hepatic portal vein and their importance for glucose handling by the liver and the brain and the systemic response to hypoglycemia. As liver diseases are on the rise globally, and there are intriguing associations between liver diseases and mental illnesses, it will be important to further dissect and identify both neural and humoral pathways that mediate hepatocyte-specific signals to relevant brain areas. The question of whether and how sensations from the liver contribute to interoceptive self-awareness has not yet been explored.
Language	English
Publishing date	2024-03-29
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2024.103174
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Article: The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model.

Spann, Redin A / Morrison, Christopher D / den Hartigh, Laura J

Frontiers in endocrinology

2022 Volume 12, Page(s) 802541

Abstract: Fibroblast growth factor 21 (FGF21) is a hormone that is involved in the regulation of lipid, glucose, and energy metabolism. Pharmacological FGF21 administration promotes weight loss and improves insulin sensitivity in rodents, non-human primates, and ... ...

Abstract	Fibroblast growth factor 21 (FGF21) is a hormone that is involved in the regulation of lipid, glucose, and energy metabolism. Pharmacological FGF21 administration promotes weight loss and improves insulin sensitivity in rodents, non-human primates, and humans. However, pharmacologic effects of FGF21 likely differ from its physiological effects. Endogenous FGF21 is produced by many cell types, including hepatocytes, white and brown adipocytes, skeletal and cardiac myocytes, and pancreatic beta cells, and acts on a diverse array of effector tissues such as the brain, white and brown adipose tissue, heart, and skeletal muscle. Different receptor expression patterns dictate FGF21 function in these target tissues, with the primary effect to coordinate responses to nutritional stress. Moreover, different nutritional stimuli tend to promote FGF21 expression from different tissues; i.e., fasting induces hepatic-derived FGF21, while feeding promotes white adipocyte-derived FGF21. Target tissue effects of FGF21 also depend on its capacity to enter the systemic circulation, which varies widely from known FGF21 tissue sources in response to various stimuli. Due to its association with obesity and non-alcoholic fatty liver disease, the metabolic effects of endogenously produced FGF21 during the pathogenesis of these conditions are not well known. In this review, we will highlight what is known about endogenous tissue-specific FGF21 expression and organ cross-talk that dictate its diverse physiological functions, with particular attention given to FGF21 responses to nutritional stress. The importance of the particular experimental design, cellular and animal models, and nutritional status in deciphering the diverse metabolic functions of endogenous FGF21 cannot be overstated.
MeSH term(s)	Adipocytes/metabolism ; Animals ; Fibroblast Growth Factors/genetics ; Fibroblast Growth Factors/metabolism ; Gene Editing ; Gene Expression ; Humans ; Liver/metabolism ; Metabolic Diseases/metabolism ; Metabolic Diseases/therapy ; Models, Animal ; Muscle, Skeletal/metabolism ; Pancreas/metabolism ; Stress, Physiological
Chemical Substances	fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2022-01-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.802541
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Article ; Online: The Protein Leverage Hypothesis: A 2019 Update for Obesity.

Hill, Cristal M / Morrison, Christopher D

Obesity (Silver Spring, Md.)

2019 Volume 27, Issue 8, Page(s) 1221

MeSH term(s)	Dietary Proteins ; Epidemics ; Humans ; Obesity/epidemiology
Chemical Substances	Dietary Proteins
Language	English
Publishing date	2019-07-23
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.22568
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Article ; Online: Dietary branched chain amino acids and metabolic health: when less is more.

Hill, Cristal M / Morrison, Christopher D

The Journal of physiology

2018 Volume 596, Issue 4, Page(s) 555–556

MeSH term(s)	Amino Acids, Branched-Chain ; Blood Glucose ; Insulin
Chemical Substances	Amino Acids, Branched-Chain ; Blood Glucose ; Insulin
Language	English
Publishing date	2018-01-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP275613
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Article ; Online: The obesity epidemic in the face of homeostatic body weight regulation: What went wrong and how can it be fixed?

Berthoud, Hans-Rudolf / Morrison, Christopher D / Münzberg, Heike

Physiology & behavior

2020 Volume 222, Page(s) 112959

Abstract: Ever since the pioneering discoveries in the mid nineteen hundreds, the hypothalamus was recognized as a crucial component of the neural system controlling appetite and energy balance. The new wave of neuron-specific research tools has confirmed this key ...

Abstract	Ever since the pioneering discoveries in the mid nineteen hundreds, the hypothalamus was recognized as a crucial component of the neural system controlling appetite and energy balance. The new wave of neuron-specific research tools has confirmed this key role of the hypothalamus and has delineated many other brain areas to be part of an expanded neural system sub serving these crucial functions. However, despite significant progress in defining this complex neural circuitry, many questions remain. One of the key questions is why the sophisticated body weight regulatory system is unable to prevent the rampant obesity epidemic we are experiencing. Why are pathologically obese body weight levels defended, and what can we do about it? Here we try to find answers to these questions by 1) reminding the reader that the neural controls of ingestive behavior have evolved in a demanding, restrictive environment and encompass much of the brain's major functions, far beyond the hypothalamus and brainstem, 2) hypothesizing that the current obesogenic environment impinges mainly on a critical pathway linking hypothalamic areas with the motivational and reward systems to produce uncompensated hyperphagia, and 3) proposing adequate strategies for prevention and treatment.
MeSH term(s)	Body Weight ; Eating ; Energy Metabolism ; Epidemics ; Homeostasis ; Humans ; Hypothalamus ; Obesity/epidemiology
Language	English
Publishing date	2020-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2020.112959
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Article: The obesity epidemic in the face of homeostatic body weight regulation: What went wrong and how can it be fixed?

Berthoud, Hans-Rudolf / Morrison, Christopher D / Münzberg, Heike

Physiology & behavior. 2020 Aug. 01, v. 222

2020

Abstract	Ever since the pioneering discoveries in the mid nineteen hundreds, the hypothalamus was recognized as a crucial component of the neural system controlling appetite and energy balance. The new wave of neuron-specific research tools has confirmed this key role of the hypothalamus and has delineated many other brain areas to be part of an expanded neural system sub serving these crucial functions. However, despite significant progress in defining this complex neural circuitry, many questions remain. One of the key questions is why the sophisticated body weight regulatory system is unable to prevent the rampant obesity epidemic we are experiencing. Why are pathologically obese body weight levels defended, and what can we do about it? Here we try to find answers to these questions by 1) reminding the reader that the neural controls of ingestive behavior have evolved in a demanding, restrictive environment and encompass much of the brain's major functions, far beyond the hypothalamus and brainstem, 2) hypothesizing that the current obesogenic environment impinges mainly on a critical pathway linking hypothalamic areas with the motivational and reward systems to produce uncompensated hyperphagia, and 3) proposing adequate strategies for prevention and treatment.
Keywords	appetite ; body weight changes ; brain stem ; energy balance ; environmental factors ; hypothalamus ; obesity ; overeating
Language	English
Dates of publication	2020-0801
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-light
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2020.112959
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Learning of food preferences: mechanisms and implications for obesity & metabolic diseases.

Berthoud, Hans-Rudolf / Morrison, Christopher D / Ackroff, Karen / Sclafani, Anthony

International journal of obesity (2005)

2021 Volume 45, Issue 10, Page(s) 2156–2168

Abstract: Omnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and ... ...

Abstract	Omnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut-brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.
MeSH term(s)	Animals ; Disease Models, Animal ; Food Preferences/psychology ; Learning ; Metabolic Diseases/diet therapy ; Metabolic Diseases/physiopathology ; Mice, Inbred C57BL/metabolism ; Obesity/diet therapy ; Obesity/physiopathology ; Mice
Language	English
Publishing date	2021-07-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-021-00894-3
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Zs.A 1325: Show issues

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Article ; Online: Regulation of body weight: Lessons learned from bariatric surgery.

Albaugh, Vance L / He, Yanlin / Münzberg, Heike / Morrison, Christopher D / Yu, Sangho / Berthoud, Hans-Rudolf

Molecular metabolism

2022 Volume 68, Page(s) 101517

Abstract: Background: Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the ... ...

Abstract	Background: Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved. Scope of review: The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents. Major conclusions: Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.
MeSH term(s)	Animals ; Humans ; Obesity, Morbid/metabolism ; Bariatric Surgery/adverse effects ; Obesity/metabolism ; Gastric Bypass/methods ; Weight Loss/physiology
Language	English
Publishing date	2022-05-26
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2022.101517
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Article: Use of Bowel in Reconstructive Urology: What a Colorectal Surgeon Should Know.

Morrison, Christopher D / Kielb, Stephanie J

Clinics in colon and rectal surgery

2017 Volume 30, Issue 3, Page(s) 207–214

Abstract: Urologists routinely use bowel in the reconstruction of the urinary tract. With an increasing prevalence of urinary diversions, it is important for surgeons to have a basic understanding of varied use and configuration of bowel segments in urinary tract ... ...

Abstract	Urologists routinely use bowel in the reconstruction of the urinary tract. With an increasing prevalence of urinary diversions, it is important for surgeons to have a basic understanding of varied use and configuration of bowel segments in urinary tract reconstruction that may be encountered during abdominal surgery. The aim of this review article is to provide an overview of the various reconstructive urological surgeries requiring bowel and to guide physicians on how to manage these patients with urinary diversions.
Language	English
Publishing date	2017-05-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2048635-2
ISSN	1531-0043
ISSN	1531-0043
DOI	10.1055/s-0037-1598162
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Zs.A 3931: Show issues

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Article ; Online: The Vagus Nerve Mediates Gut-Brain Response to Duodenal Nutrient Administration.

Ross, Robert C / He, Yanlin / Townsend, R Leigh / Schauer, Philip R / Berthoud, Hans-Rudolph / Morrison, Christopher D / Albaugh, Vance L

The American surgeon

2023 Volume 89, Issue 8, Page(s) 3600–3602

Abstract: Background: Obesity contributes significant disease burden worldwide, including diabetes, cardiovascular disease, and cancer. While bariatric surgery is the most effective and durable obesity treatment, the mechanisms underlying its effects remain ... ...

Abstract	Background: Obesity contributes significant disease burden worldwide, including diabetes, cardiovascular disease, and cancer. While bariatric surgery is the most effective and durable obesity treatment, the mechanisms underlying its effects remain unknown. Although neuro-hormonal mechanisms have been suspected to mediate at least some of the gut-brain axis changes following bariatric surgery, studies examining the intestine and its regionally specific post-gastric alterations to these signals remain unclear. Materials and methods: Vagus nerve recording was performed following the implantation of duodenal feeding tubes in mice. Testing conditions and measurements were made under anesthesia during baseline, nutrient or vehicle solution delivery, and post-delivery. Solutions tested included water, glucose, glucose with an inhibitor of glucose absorption (phlorizin), and a hydrolyzed protein solution. Results: Vagus nerve signaling was detectable from the duodenum and exhibited stable baseline activity without responding to osmotic pressure gradients. Duodenal-delivered glucose and protein robustly increased vagus nerve signaling, but increased signaling was abolished during the co-administration of glucose and phlorizin. Discussion: Gut-brain communication via the vagus nerve emanating from the duodenum is nutrient sensitive and easily measurable in mice. Examination of these signaling pathways may help elucidate how the nutrient signals from the intestine are altered when applied to obesity and bariatric surgery mouse models. Future studies will address quantifying the changes in neuroendocrine nutrient signals in health and obesity, with specific emphasis on identifying the changes associated with bariatric surgery and other gastrointestinal surgery.
MeSH term(s)	Mice ; Animals ; Phlorhizin/metabolism ; Phlorhizin/pharmacology ; Brain ; Duodenum/surgery ; Bariatric Surgery ; Glucose/metabolism ; Glucose/pharmacology ; Obesity ; Nutrients ; Vagus Nerve/metabolism
Chemical Substances	Phlorhizin (CU9S17279X) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
DOI	10.1177/00031348231161680
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