Academic Research

20 years in metabolism science.

PhD in Physiology, Endocrinology and Metabolism. Two postdoctoral fellowships. Forty-plus peer-reviewed publications. The practice is built on what actually survives scientific scrutiny.

40+

Peer-Reviewed
Publications

2,169

Total
Citations

Years in Metabolism
Science

Postdoctoral
Fellowships

Background

The science behind the practice.

I completed my PhD in Physiology, Endocrinology and Metabolism at São Paulo State University (UNESP) in Brazil, studying how fructose-rich diets drive fatty liver, insulin resistance and metabolic syndrome, and how different exercise protocols prevent and reverse them.

I then moved to the University of Campinas (UNICAMP) for a first postdoctoral fellowship, on how exercise changes insulin and leptin signalling in muscle, liver and the brain. At the University of British Columbia I was a postdoctoral fellow in the Department of Cellular and Physiological Sciences, then a research associate at the Centre for Blood Research, working on how chronically high insulin itself drives weight gain and insulin resistance, in genetic mouse models and human muscle samples.

The gap between peer-reviewed evidence and clinical coaching practice is enormous. Twenty years across the lab and the training floor taught me exactly how wide it is.

I've published in Cell Metabolism, Nature Communications, EBioMedicine, the FASEB Journal, Scientific Reports, Nutrients and the American Journal of Physiology, among other indexed journals. My research focuses on insulin and insulin resistance, fructose and fatty liver, skeletal muscle, and the role of structured exercise in metabolic disease.

Research & Teaching

What the lab and the lecture hall covered.

Skeletal Muscle Metabolism

How endurance and strength exercise change skeletal muscle: insulin signalling, GLUT4 (Slc2a4), glycogen and glucose uptake.

Insulin Sensitivity & Resistance

How chronically high insulin drives insulin resistance, and how strength and aerobic training restore insulin action in muscle, liver and the brain's appetite centre, in animal models and human muscle.

Fructose & Fatty Liver

How fructose-rich diets raise liver fat, tissue lipids and blood lipids, and how training at different intensities brings them back down.

Fat Tissue & Obesity

Why high insulin drives diet-induced obesity, and how lowering insulin changes fat tissue depot by depot (thermogenic UCP1 and mitochondrial proteins).

Hormonal Physiology

Years of lecturing on the physiology of testosterone, estrogen, cortisol and the thyroid hormones: the endocrine system behind every coaching decision.

Metabolic Disease Prevention

Exercise and nutrition against metabolic syndrome, fatty liver and type 2 diabetes, from animal models to a randomized trial in people with type 2 diabetes.

Institutions

Where the research was done.

PhD

São Paulo State University (UNESP) Endocrine physiology · São Paulo, Brazil

Postdoc I

University of Campinas (UNICAMP) School of Applied Sciences · Limeira, Brazil

Postdoc II

University of British Columbia (UBC) Department of Cellular and Physiological Sciences · Vancouver, BC · 2017–2019

Research Associate

University of British Columbia (UBC) Centre for Blood Research · Vancouver, BC · 2019–2020

Practice

Team Botezelli (Jose Diego Botezelli PhD Institute Inc.) Port Coquitlam, BC · Online worldwide · 2020–present

Selected Publications

Research that built the practice.

Nine papers from the indexed work — each one directly connected to a coaching decision. Full list on Google Scholar.

2012 Cell Metabolism IF 29

Hyperinsulinemia drives diet-induced obesity independently of brain insulin production

Mehran AE, Templeman NM, Brigidi GS, Lim GE, Chu KY, Hu X, Botezelli JD, et al.

666 citations

The finding

Using genetic mouse models with reduced insulin production, this team showed that hyperinsulinemia is not just a consequence of obesity but can drive it. Mice that could not raise their insulin on a high-fat diet were protected from diet-induced obesity, burning more energy through Ucp1 in white fat. The paper challenged the view that insulin resistance must come first and reframed how the field thinks about the obesity-insulin cycle.

How it shapes the practice

These were mouse experiments, so the human translation is an interpretation: if insulin itself can push fat storage, eating patterns that keep insulin high all day work against fat loss even at reasonable calories. That reasoning shapes how Diego Botezelli plans carbohydrate timing and meal structure for clients with insulin-resistance markers.

2022 Nature Communications IF 16

Beta-cell specific Insr deletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance

Skovsø S, Panzhinskiy E, Kolic J, Cen HH, Dionne DA, Dai XQ, ... Botezelli JD, et al.

51 citations

The finding

A decade after the Cell Metabolism paper, the team revisited the same biology with a precision-genetics tool in mice. Deleting the insulin receptor only in pancreatic beta cells increased insulin release and improved glucose tolerance, a counterintuitive result. The benefit lasted to 39 weeks in female mice but was absent in older males and in mice on a high-fat diet, where whole-body insulin resistance masked it.

How it shapes the practice

In Diego Botezelli's coaching experience, pre-diabetic clients often show high fasting insulin with still-normal blood glucose. That is the window to act, and this paper shows how tightly beta-cell insulin signalling and whole-body insulin sensitivity are linked.

2017 Nutrients IF 6

Fructose consumption in the development of obesity and the effects of different protocols of physical exercise on the hepatic metabolism

Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, et al.

148 citations

The finding

A review written as second author, co-designed and co-written. It brings together the evidence on how dietary fructose drives obesity, fatty liver, hepatic insulin resistance and metabolic syndrome, and how aerobic, strength or combined training attenuate that damage by improving blood and liver lipids and inflammation markers.

How it shapes the practice

Fructose is handled differently from glucose: the liver takes up most of it and turns more of it into fat. Aerobic and strength training both counter that, which is why the BTZ Weight Well and Lean & Strong programs combine them for clients carrying visceral fat.

2016 Scientific Reports IF 4 First Author

Strength training prevents hyperinsulinemia, insulin resistance, and inflammation independent of weight loss in fructose-fed animals

Botezelli JD, Coope A, Ghezzi AC, Cambri LT, Moura LP, Scariot PPM, et al.

61 citations

The finding

A study led as first author, in Wistar rats fed a high-fructose diet, comparing aerobic, strength and combined training. All three lowered inflammatory signalling in liver and muscle. Strength training prevented hyperinsulinemia and insulin resistance with no change in body weight or food intake, and had the largest effect on liver fat.

How it shapes the practice

This study shaped the BTZ Lean & Strong protocol. Most clients arrive thinking weight loss is the goal; here the metabolic benefits of strength training appeared without any change on the scale, which is why the scale is only one of the numbers we track.

2024 EBioMedicine IF 10

CD248 promotes insulin resistance by binding to the insulin receptor and dampening its insulin-induced autophosphorylation

Benedet PO, Safikhan NS, Pereira MJ, Lum BM, Botezelli JD, Kuo CH, et al.

8 citations

The finding

A collaboration showing how CD248, a protein on the surface of fat cells and their precursors, brakes insulin signalling: it binds the insulin receptor and dampens its activation, contributing to insulin resistance in fat tissue. Shown in mice and confirmed in human fat tissue, it adds a candidate target for metabolic disease therapy.

How it shapes the practice

Insulin resistance has more than one molecular cause, one plausible reason clients with similar weight and habits respond differently. Coaching has to track the markers, not the slogans.

2018 American Journal of Physiology — Regulatory, Integrative and Comparative Physiology IF 3

The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial

Myette-Côté É, Durrer C, Neudorf H, Bammert TD, Botezelli JD, et al.

113 citations

The finding

A small randomized crossover trial in 11 people with type 2 diabetes, with three 4-day diet periods. A low-carb, high-fat diet lowered 4-day average glucose by 12% compared with a low-fat diet; adding 15-minute walks after meals lowered it a further 5%. Inflammation markers did not improve more than on the low-fat control.

How it shapes the practice

A 15-minute walk after meals is one of the most underused tools for clients managing type 2 diabetes or pre-diabetes. In this trial it added a measurable drop in glucose on top of the diet within 4 days.

2020 American Journal of Physiology — Endocrinology and Metabolism IF 5 First Author

Adipose depot-specific upregulation of Ucp1 or mitochondrial oxidative complex proteins are early consequences of genetic insulin reduction in mice

Botezelli JD, Overby P, Lindo L, Wang S, Haïda O, Lim GE, et al.

17 citations

The finding

Another paper led as first author, in mice. Four weeks of genetically lowered insulin changed fat depots in different ways, before any change in body weight: Ucp1, a marker of thermogenic 'browning', rose in some depots (in mesenteric white fat and brown fat only on a high-fat diet), while others upregulated mitochondrial oxidative proteins. Body fat isn't one tissue; it behaves like several.

How it shapes the practice

When a client asks why the weight comes off everywhere except the belly, there is a biological basis: in this study visceral, subcutaneous and brown fat responded to lower insulin in different ways. These were mice, but fat depots behaving differently is well documented in people too.

2023 Cellular and Molecular Life Sciences IF 8 Co-First Author

Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice

Muñoz VR & Botezelli JD (co-first authors), Gaspar RC, da Rocha AL, Vieira RFL, Crisol BM, et al.

9 citations

The finding

A study co-led as shared first author, in mice with reduced GLUT4 (Slc2a4+/-) that develop high insulin and glucose on a normal diet. Five days of either endurance or strength training improved muscle glucose uptake and whole-body glucose control. Only endurance training improved muscle mitochondrial activity; the strength protocol acted more through protein-synthesis signalling.

How it shapes the practice

Each kind of training sends muscle a different signal: in this study only endurance work improved mitochondria. That is why BTZ programs include both strength and conditioning rather than one of them.

2022 FASEB Journal IF 5

Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance

Cen HH, Hussein B, Botezelli JD, Wang S, Zhang JA, Noursadeghi N, et al.

35 citations

The finding

A study comparing skeletal muscle gene expression in human samples and in mouse models of chronically high insulin. In both, insulin-receptor mRNA was lower when insulin was high (about 20% lower in the mouse model), suggesting that chronically high insulin may reduce the receptor itself, a possible self-reinforcing loop. The human data are associations; the cause-and-effect work was done in mouse cells and mice.

How it shapes the practice

Insulin resistance may partly sustain itself once insulin stays high for long, which is one reason we act early on high fasting insulin rather than waiting for blood glucose to rise.

Publications Database

Read the original research.

The complete indexed publication list — with citations, DOIs, and journal links — is maintained on Google Scholar. Every paper is linked to its original source.

40+ publications · 2,169 citations

View on Google Scholar → Book a Consultation